Generic placeholder image

Current Immunology Reviews (Discontinued)


ISSN (Print): 1573-3955
ISSN (Online): 1875-631X

Review Article

Mucosal Immunity in HIV/SIV Infection: T Cells, B Cells and Beyond

Author(s): Barbara L. Shacklett*

Volume 15, Issue 1, 2019

Page: [63 - 75] Pages: 13

DOI: 10.2174/1573395514666180528081204

Price: $65


As our understanding of mucosal immunity increases, it is becoming clear that the host response to HIV-1 is more complex and nuanced than originally believed. The mucosal landscape is populated with a variety of specialized cell types whose functions include combating infectious agents while preserving commensal microbiota, maintaining barrier integrity, and ensuring immune homeostasis. Advances in multiparameter flow cytometry, gene expression analysis and bioinformatics have allowed more detailed characterization of these cell types and their roles in host defense than was previously possible. This review provides an overview of existing literature on immunity to HIV-1 and SIVmac in mucosal tissues of the female reproductive tract and the gastrointestinal tract, focusing on major effector cell populations and briefly summarizing new information on tissue-resident memory T cells, Treg, Th17, Th22 and innate lymphocytes (ILC), subsets that have been studied primarily in the gastrointestinal mucosa.

Keywords: HIV-1, SIV, mucosa, gut, T-cell, adaptive, innate.

Chenine AL, Siddappa NB, Kramer VG, et al. Relative transmissibility of an R5 clade C simian-human immunodeficiency virus across different mucosae in macaques parallels the relative risks of sexual HIV-1 transmission in humans via different routes. J Infect Dis 2010; 201(8): 1155-63.
Iwasaki A. Antiviral immune responses in the genital tract: Clues for vaccines. Nat Rev Immunol 2010; 10(10): 699-711.
Pudney J, Quayle AJ, Anderson DJ. Immunological microenvironments in the human vagina and cervix: Mediators of cellular immunity are concentrated in the cervical transformation zone. Biol Reprod 2005; 73(6): 1253-63.
Grande G, Milardi D, Vincenzoni F, et al. Proteomic characterization of the qualitative and quantitative differences in cervical mucus composition during the menstrual cycle. Mol Biosyst 2015; 11(6): 1717-25.
Lee DC, Hassan SS, Romero R, et al. Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy. J Proteomics 2011; 74(6): 817-28.
Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 2000; 74(13): 6087-95.
Zhang Z, Schuler T, Zupancic M, et al. Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 1999; 286(5443): 1353-7.
Miller CJ, Alexander NJ, Vogel P, Anderson J, Marx PA. Mechanism of genital transmission of SIV: A hypothesis based on transmission studies and the location of SIV in the genital tract of chronically infected female rhesus macaques. J Med Primatol 1992; 21(2-3): 64-8.
Padian NS, van der Straten A, Ramjee G, et al. Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial. Lancet 2007; 370(9583): 251-61.
Ballweber L, Robinson B, Kreger A, et al. Vaginal Langerhans cells nonproductively transporting HIV-1 mediate infection of T cells. J Virol 2011; 85(24): 13443-7.
Hladik F, McElrath MJ. Setting the stage: Host invasion by HIV. Nat Rev Immunol 2008; 8(6): 447-57.
Hladik F, Sakchalathorn P, Ballweber L, et al. Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 2007; 26(2): 257-70.
Shen R, Kappes JC, Smythies LE, Richter HE, Novak L, Smith PD. Vaginal myeloid dendritic cells transmit founder HIV-1. J Virol 2014; 88(13): 7683-8.
Shen R, Richter HE, Smith PD. Interactions between HIV-1 and mucosal cells in the female reproductive tract. Am J Reprod Immunol 2014; 71(6): 608-17.
Stieh DJ, Matias E, Xu H, et al. Th17 cells are preferentially infected very early after vaginal transmission of SIV in macaques. Cell Host Microbe 2016; 19(4): 529-40.
Rodriguez-Garcia M, Barr FD, Crist SG, Fahey JV, Wira CR. Phenotype and susceptibility to HIV infection of CD4+ Th17 cells in the human female reproductive tract. Mucosal Immunol 2014; 7(6): 1375-85.
Shanmugasundaram U, Critchfield JW, Pannell J, et al. Phenotype and functionality of CD4+ and CD8+ T cells in the upper reproductive tract of healthy premenopausal women. Am J Reprod Immunol 2014; 71(2): 95-108.
Stieh DJ, Maric D, Kelley ZL, et al. Vaginal challenge with an SIV-based dual reporter system reveals that infection can occur throughout the upper and lower female reproductive tract. PLoS Pathog 2014; 10(10): e1004440.
Shen Z, Rodriguez-Garcia M, Ochsenbauer C, Wira CR. Characterization of immune cells and infection by HIV in human ovarian tissues. Am J Reprod Immunol 2017; 78(1): e12687.
Louissaint NA, Fuchs EJ, Bakshi RP, et al. Distribution of cell-free and cell-associated HIV surrogates in the female genital tract after simulated vaginal intercourse. J Infect Dis 2012; 205(5): 725-32.
El Costa H, Quillay H, Marlin R, et al. The local environment orchestrates mucosal decidual macrophage differentiation and substantially inhibits HIV-1 replication. Mucosal Immunol 2016; 9(3): 634-46.
Quillay H, El Costa H, Marlin R, et al. Distinct characteristics of endometrial and decidual macrophages and regulation of their permissivity to HIV-1 infection by SAMHD1. J Virol 2015; 89(2): 1329-39.
Rahangdale L, De Paris K, Kashuba AD, et al. Immunologic, virologic, and pharmacologic characterization of the female upper genital tract in HIV-infected women. J Acquir Immune Defic Syndr 2015; 68(4): 420-4.
Reynolds MR, Rakasz E, Skinner PJ, et al. CD8+ T-lymphocyte response to major immunodominant epitopes after vaginal exposure to simian immunodeficiency virus: Too late and too little. J Virol 2005; 79(14): 9228-35.
Li Q, Skinner PJ, Ha SJ, et al. Visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection. Science 2009; 323(5922): 1726-9.
Masopust D. Developing an HIV cytotoxic T-lymphocyte vaccine: issues of CD8 T-cell quantity, quality and location. J Intern Med 2009; 265(1): 125-37.
Lohman BL, Miller CJ, McChesney MB. Antiviral cytotoxic T lymphocytes in vaginal mucosa of simian immunodeficiency virus-infected rhesus macaques. J Immunol 1995; 155(12): 5855-60.
Musey L, Ding Y, Cao J, et al. Ontogeny and specificities of mucosal and blood human immunodeficiency virus type 1-specific CD8(+) cytotoxic T lymphocytes. J Virol 2003; 77(1): 291-300.
Musey L, Hu Y, Eckert L, Christensen M, Karchmer T, McElrath MJ. HIV-1 induces cytotoxic T lymphocytes in the cervix of infected women. J Exp Med 1997; 185(2): 293-303.
Bere A, Denny L, Burgers WA, Passmore JA. Polyclonal expansion of cervical cytobrush-derived T cells to investigate HIV-specific responses in the female genital tract. Immunology 2010; 130(1): 23-33.
Bere A, Denny L, Hanekom W, Burgers WA, Passmore JA. Comparison of polyclonal expansion methods to improve the recovery of cervical cytobrush-derived T cells from the female genital tract of HIV-infected women. J Immunol Methods 2010; 354(1-2): 68-79.
McKinnon LR, Hughes SM, De Rosa SC, et al. Optimizing viable leukocyte sampling from the female genital tract for clinical trials: an international multi-site study. PLoS One 2014; 9(1): e85675.
Gumbi PP, Nkwanyana NN, Bere A, et al. Impact of mucosal inflammation on cervical human immunodeficiency virus (HIV-1)-specific CD8 T-cell responses in the female genital tract during chronic HIV infection. J Virol 2008; 82(17): 8529-36.
Ferre AL, Hunt PW, Critchfield JW, et al. Mucosal immune responses to HIV-1 in elite controllers: A potential correlate of immune control. Blood 2009; 113(17): 3978-89.
Makedonas G, Betts MR. Polyfunctional analysis of human t cell responses: importance in vaccine immunogenicity and natural infection. Springer Semin Immunopathol 2006; 28(3): 209-19.
Bere A, Denny L, Naicker P, Burgers WA, Passmore JA. HIV-specific T-cell responses detected in the genital tract of chronically HIV-infected women are largely monofunctional. Immunology 2013; 139(3): 342-51.
Nkwanyana NN, Gumbi PP, Roberts L, et al. Impact of human immunodeficiency virus 1 infection and inflammation on the composition and yield of cervical mononuclear cells in the female genital tract. Immunology 2009; 128(1)(Suppl.): e746-57.
Mkhize NN, Gumbi PP, Liebenberg LJ, et al. Persistence of genital tract T cell responses in HIV-infected women on highly active antiretroviral therapy. J Virol 2010; 84(20): 10765-72.
Eschenbach DA, Thwin SS, Patton DL, et al. Influence of the normal menstrual cycle on vaginal tissue, discharge, and microflora. Clin Infect Dis 2000; 30(6): 901-7.
Poonia B, Walter L, Dufour J, Harrison R, Marx PA, Veazey RS. Cyclic changes in the vaginal epithelium of normal rhesus macaques. J Endocrinol 2006; 190(3): 829-35.
Wira CR, Rodriguez-Garcia M, Patel MV. The role of sex hormones in immune protection of the female reproductive tract. Nat Rev Immunol 2015; 15(4): 217-30.
Morrison CS, Chen PL, Kwok C, et al. Hormonal contraception and the risk of HIV acquisition: An individual participant data meta-analysis. PLoS Med 2015; 12(1): e1001778.
Ralph LJ, McCoy SI, Shiu K, Padian NS. Hormonal contraceptive use and women’s risk of HIV acquisition: A meta-analysis of observational studies. Lancet Infect Dis 2015; 15(2): 181-9.
Achilles SL, Creinin MD, Stoner KA, Chen BA, Meyn L, Hillier SL. Changes in genital tract immune cell populations after initiation of intrauterine contraceptionAm J Obstet Gynecol 2014;¶ 211(5): 489 e1-9
Achilles SL, Hillier SL. The complexity of contraceptives: Understanding their impact on genital immune cells and vaginal microbiota. AIDS 2013; 27(Suppl. 1): S5-S15.
Byrne EH, Anahtar MN, Cohen KE, et al. Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: A prospective cohort study. Lancet Infect Dis 2016; 16(4): 441-8.
Smith-McCune KK, Hilton JF, Shanmugasundaram U, et al. Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: implications for HIV susceptibility. Mucosal Immunol 2017; 10(5): 1270-8.
Wira CR, Fahey JV. A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 2008; 22(15): 1909-17.
Wira CR, Fahey JV, Rodriguez-Garcia M, Shen Z, Patel MV. Regulation of mucosal immunity in the female reproductive tract: The role of sex hormones in immune protection against sexually transmitted pathogens. Am J Reprod Immunol 2014; 72(2): 236-58.
White HD, Yeaman GR, Givan AL, Wira CR. Mucosal immunity in the human female reproductive tract: Cytotoxic T lymphocyte function in the cervix and vagina of premenopausal and postmenopausal women. Am J Reprod Immunol 1997; 37(1): 30-8.
Yeaman GR, Guyre PM, Fanger MW, et al. Unique CD8+ T cell-rich lymphoid aggregates in human uterine endometrium. J Leukoc Biol 1997; 61(4): 427-35.
White HD, Musey LK, Andrews MM, et al. Human immunodeficiency virus-specific and CD3-redirected cytotoxic T lymphocyte activity in the human female reproductive tract: lack of correlation between mucosa and peripheral blood. J Infect Dis 2001; 183(6): 977-83.
Veazey RS, DeMaria M, Chalifoux LV, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 1998; 280(5362): 427-31.
Brenchley JM, Douek DC. The mucosal barrier and immune activation in HIV pathogenesis. Curr Opin HIV AIDS 2008; 3(3): 356-61.
Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12(12): 1365-71.
Fritsch H, Zehm S, Illig R, Moser P, Aigner F. New insights into the development and differentiation of the human anorectal epithelia. Are there clinical consequences? Int J Colorectal Dis 2010; 25(10): 1231-42.
McElrath MJ, Smythe K, Randolph-Habecker J, et al. Comprehensive assessment of HIV target cells in the distal human gut suggests increasing HIV susceptibility toward the anus. J Acquir Immune Defic Syndr 2013; 63(3): 263-71.
Poles MA, Elliott J, Taing P, Anton PA, Chen IS. A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection. J Virol 2001; 75(18): 8390-9.
Preza GC, Tanner K, Elliott J, Yang OO, Anton PA, Ochoa MT. Antigen-presenting cell candidates for HIV-1 transmission in human distal colonic mucosa defined by CD207 dendritic cells and CD209 macrophages. AIDS Res Hum Retroviruses 2014; 30(3): 241-9.
Shacklett BL, Anton PA. HIV infection and gut mucosal immune function: Updates on pathogenesis with implications for management and intervention. Curr Infect Dis Rep 2010; 12(1): 19-27.
Louissaint NA, Nimmagadda S, Fuchs EJ, et al. Distribution of cell-free and cell-associated HIV surrogates in the colon after simulated receptive anal intercourse in men who have sex with men. J Acquir Immune Defic Syndr 2012; 59(1): 10-7.
Baggaley RF, White RG, Boily MC. HIV transmission risk through anal intercourse: Systematic review, meta-analysis and implications for HIV prevention. Int J Epidemiol 2010; 39(4): 1048-63.
Gorbach PM, Manhart LE, Hess KL, Stoner BP, Martin DH, Holmes KK. Anal intercourse among young heterosexuals in three sexually transmitted disease clinics in the United States. Sex Transm Dis 2009; 36(4): 193-8.
Shacklett BL, Beadle TJ, Pacheco PAG, et al. Isolation of cytomegalovirus-specific cytotoxic T-lymphocytes from Gut-Associated Lymphoid Tissue (GALT) of HIV type 1-infected subjects. AIDS Res Hum Retroviruses 2000; 16(12): 1157-62.
Shacklett BL, Beadle TJ, Pacheco PA, et al. Characterization of HIV-1-specific cytotoxic T lymphocytes expressing the mucosal lymphocyte integrin CD103 in rectal and duodenal lymphoid tissue of HIV-1-infected subjects. Virology 2000; 270(2): 317-27.
Shacklett BL, Cox CA, Sandberg JK, Stollman NH, Jacobson MA, Nixon DF. Trafficking of human immunodeficiency virus type 1-specific CD8+ T cells to gut-associated lymphoid tissue during chronic infection. J Virol 2003; 77(10): 5621-31.
Ibarrondo FJ, Anton PA, Fuerst M, et al. Parallel human immunodeficiency virus type 1-specific CD8+ T-lymphocyte responses in blood and mucosa during chronic infection. J Virol 2005; 79(7): 4289-97.
Critchfield JW, Young DH, Hayes TL, et al. Magnitude and complexity of rectal mucosa HIV-1-specific CD8+ T-cell responses during chronic infection reflect clinical status. PLoS One 2008; 3(10): e3577.
Critchfield JW, Lemongello D, Walker DH, et al. Multifunctional Human Immunodeficiency Virus (HIV) gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. J Virol 2007; 81(11): 5460-71.
Ferre AL, Lemongello D, Hunt PW, et al. Immunodominant HIV-specific CD8+ T-cell responses are common to blood and gastrointestinal mucosa, and Gag-specific responses dominate in rectal mucosa of HIV controllers. J Virol 2010; 84(19): 10354-65.
Ferre AL, Hunt PW, McConnell DH, et al. HIV controllers with HLA-DRB1*13 and HLA-DQB1*06 alleles have strong, polyfunctional mucosal CD4+ T-cell responses. J Virol 2010; 84(21): 11020-9.
Fellay J, Ge D, Shianna KV, et al. Common genetic variation and the control of HIV-1 in humans. PLoS Genet 2009; 5(12): e1000791.
International HIVCS. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010; 330(6010): 1551-7.
Shacklett BL, Cox CA, Quigley MF, et al. Abundant expression of granzyme A, but not perforin, in granules of CD8+ T cells in GALT: Implications for immune control of HIV-1 infection. J Immunol 2004; 173(1): 641-8.
Kiniry BE, Ganesh A, Critchfield JW, et al. Predominance of weakly cytotoxic, T-betLowEomesNeg CD8+ T-cells in human gastrointestinal mucosa: Implications for HIV infection. Mucosal Immunol 2017; 10(4): 1008-20.
Casey KA, Fraser KA, Schenkel JM, et al. Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues. J Immunol 2012; 188(10): 4866-75.
Rosato PC, Beura LK, Masopust D. Tissue resident memory T cells and viral immunity. Curr Opin Virol 2017; 22: 44-50.
Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D. T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 2014; 346(6205): 98-101.
Steinert EM, Schenkel JM, Fraser KA, et al. Quantifyingmemory CD8 T cells reveals regionalization of immunosurveillance. Cell 2015; 161(4): 737-49.
Mackay LK, Rahimpour A, Ma JZ, et al. The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin. Nat Immunol 2013; 14(12): 1294-301.
Mackay LK, Stock AT, Ma JZ, et al. Long-lived epithelial immunity by Tissue-Resident Memory T (TRM) cells in the absence of persisting local antigen presentation. Proc Natl Acad Sci USA 2012; 109(18): 7037-42.
Mackay LK, Wynne-Jones E, Freestone D, et al. T-box transcription factors combine with the cytokines TGF-beta and IL-15 to control tissue-resident memory T cell fate. Immunity 2015; 43(6): 1101-11.
Carbone FR, Mackay LK, Heath WR, Gebhardt T. Distinct resident and recirculating memory T cell subsets in non-lymphoid tissues. Curr Opin Immunol 2013; 25(3): 329-33.
Mueller SN, Mackay LK. Tissue-resident memory T cells: local specialists in immune defence. Nat Rev Immunol 2016; 16(2): 79-89.
Mackay LK, Kallies A. Transcriptional regulation of tissue-resident lymphocytes. Trends Immunol 2017; 38(2): 94-103.
Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol 2003; 77(21): 11708-17.
Li Q, Duan L, Estes JD, et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 2005; 434(7037): 1148-52.
Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005; 434(7037): 1093-7.
Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med 2004; 200(6): 761-70.
Girard A, Vergnon-Miszczycha D, Depince-Berger AE, et al. Brief Report: A high rate of beta7+ gut-homing lymphocytes in HIV-infected immunological nonresponders is associated With poor CD4 T-cell recovery during suppressive HAART. J Acquir Immune Defic Syndr 2016; 72(3): 259-65.
Mavigner M, Cazabat M, Dubois M, et al. Altered CD4+ T cell homing to the gut impairs mucosal immune reconstitution in treated HIV-infected individuals. J Clin Invest 2012; 122(1): 62-9.
Allers K, Puyskens A, Epple HJ, et al. The effect of timing of antiretroviral therapy on CD4+ T-cell reconstitution in the intestine of HIV-infected patients. Mucosal Immunol 2016; 9(1): 265-74.
Deleage C, Schuetz A, Alvord WG, et al. Impact of early cART in the gut during acute HIV infection. JCI Insight 2016; 1(10): e87065.
Kok A, Hocqueloux L, Hocini H, et al. Early initiation of combined antiretroviral therapy preserves immune function in the gut of HIV-infected patients. Mucosal Immunol 2015; 8(1): 127-40.
Schuetz A, Deleage C, Sereti I, et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog 2014; 10(12): e1004543.
Cecchinato V, Franchini G. Th17 cells in pathogenic simian immunodeficiency virus infection of macaques. Curr Opin HIV AIDS 2010; 5(2): 141-5.
Sallusto F, Zielinski CE, Lanzavecchia A. Human Th17 subsets. Eur J Immunol 2012; 42(9): 2215-20.
Ciccone EJ, Greenwald JH, Lee PI, et al. CD4+ T cells, including Th17 and cycling subsets, are intact in the gut mucosa of HIV-1-infected long-term nonprogressors. J Virol 2011; 85(12): 5880-8.
Raffatellu M, Santos RL, Verhoeven DE, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 2008; 14(4): 421-8.
Gosselin A, Monteiro P, Chomont N, et al. Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J Immunol 2010; 184(3): 1604-16.
Wacleche VS, Goulet JP, Gosselin A, et al. New insights into the heterogeneity of Th17 subsets contributing to HIV-1 persistence during antiretroviral therapy. Retrovirology 2016; 13(1): 59.
Gosselin A, Wiche Salinas TR, Planas D, et al. HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. AIDS 2017; 31(1): 35-48.
Christensen-Quick A, Lafferty M, Sun L, Marchionni L, DeVico A, Garzino-Demo A. Human Th17 cells lack HIV-inhibitory RNases and are highly permissive to productive HIV infection. J Virol 2016; 90(17): 7833-47.
Belkaid Y, Tarbell K. Regulatory T cells in the control of host-microorganism interactions. Annu Rev Immunol 2009; 27: 551-89.
Kanwar B, Favre D, McCune JM. Th17 and regulatory T cells: Implications for AIDS pathogenesis. Curr Opin HIV AIDS 2010; 5(2): 151-7.
Shaw JM, Hunt PW, Critchfield JW, et al. Increased frequency of regulatory T cells accompanies increased immune activation in rectal mucosae of HIV-positive noncontrollers. J Virol 2011; 85(21): 11422-34.
Rueda CM, Velilla PA, Chougnet CA, Rugeles MT. Incomplete normalization of regulatory T-cell frequency in the gut mucosa of Colombian HIV-infected patients receiving long-term antiretroviral treatment. PLoS One 2013; 8(8): e71062.
Presicce P, Shaw JM, Miller CJ, Shacklett BL, Chougnet CA. Myeloid dendritic cells isolated from tissues of SIV-infected Rhesus macaques promote the induction of regulatory T cells. AIDS 2012; 26(3): 263-73.
Moreno-Fernandez ME, Presicce P, Chougnet CA. Homeostasis and function of regulatory T cells in HIV/SIV infection. J Virol 2012; 86(19): 10262-9.
Favre D, Lederer S, Kanwar B, et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog 2009; 5(2): e1000295.
Mellor AL, Munn DH. IDO expression by dendritic cells: Tolerance and tryptophan catabolism. Nat Rev Immunol 2004; 4(10): 762-74.
Baban B, Chandler PR, Sharma MD, et al. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol 2009; 183(4): 2475-83.
Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med 2010; 2(32): 32ra36.
Jenabian MA, El-Far M, Vyboh K, et al. Immunosuppressive tryptophan catabolism and gut mucosal dysfunction following early HIV infection. J Infect Dis 2015; 212(3): 355-66.
Klatt NR, Estes JD, Sun X, et al. Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection. Mucosal Immunol 2012; 5(6): 646-57.
Loiseau C, Requena M, Mavigner M, et al. CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6-CCL20 axis in treated HIV-1-infected individuals. Mucosal Immunol 2016; 9(5): 1137-50.
Ortiz AM, Klase ZA, DiNapoli SR, et al. IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. Mucosal Immunol 2016; 9(2): 458-67.
Vujkovic-Cvijin I, Swainson LA, Chu SN, et al. Gut-resident lactobacillus abundance associates with IDO1 inhibition and Th17 dynamics in SIV-infected macaques. Cell Reports 2015; 13(8): 1589-97.
Sonnenberg GF, Fouser LA, Artis D. Border patrol: Regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol 2011; 12(5): 383-90.
Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 2009; 10(8): 857-63.
Eyerich S, Eyerich K, Pennino D, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 2009; 119(12): 3573-85.
Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol 2009; 10(8): 864-71.
Canary LA, Vinton CL, Morcock DR, et al. Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques. J Immunol 2013; 190(6): 2959-65.
Xu H, Wang X, Veazey RS. Th17 cells coordinate with Th22 cells in maintaining homeostasis of intestinal tissues and both are depleted in SIV-infected macaques. J AIDS Clin Res 2014; 5(5): 302.
Ryan ES, Micci L, Fromentin R, et al. Loss of function of intestinal IL-17 and IL-22 producing cells contributes to inflammation and viral persistence in SIV-infected rhesus macaques. PLoS Pathog 2016; 12(2): e1005412.
Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983; 309(8): 453-8.
Shirai A, Cosentino M, Leitman-Klinman SF, Klinman DM. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J Clin Invest 1992; 89(2): 561-6.
Moir S, Fauci AS. Pathogenic mechanisms of B-lymphocyte dysfunction in HIV disease. J Allergy Clin Immunol 2008; 122(1): 12-9. quiz 20-1.
Levesque MC, Moody MA, Hwang KK, et al. Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection. PLoS Med 2009; 6(7): e1000107.
Kotler DP, Scholes JV, Tierney AR. Intestinal plasma cell alterations in acquired immunodeficiency syndrome. Dig Dis Sci 1987; 32(2): 129-38.
Raux M, Finkielsztejn L, Salmon-Ceron D, et al. Comparison of the distribution of IgG and IgA antibodies in serum and various mucosal fluids of HIV type 1-infected subjects. AIDS Res Hum Retroviruses 1999; 15(15): 1365-76.
Schneider T, Zippel T, Schmidt W, Zeitz M, Ullrich R. Secretory immunity in HIV infection. Pathobiology 1998; 66(3-4): 131-8.
Chaoul N, Burelout C, Peruchon S, et al. Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus. Retrovirology 2012; 9: 43.
Qiao X, He B, Chiu A, Knowles DM, Chadburn A, Cerutti A. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. Nat Immunol 2006; 7(3): 302-10.
Xu W, Santini PA, Sullivan JS, et al. HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits. Nat Immunol 2009; 10(9): 1008-17.
Buckner CM, Moir S, Ho J, et al. Characterization of plasmablasts in the blood of HIV-infected viremic individuals: Evidence for nonspecific immune activation. J Virol 2013; 87(10): 5800-11.
Mei HE, Yoshida T, Sime W, et al. Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood 2009; 113(11): 2461-9.
Buckner CM, Moir S, Kardava L, et al. CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation. J Allergy Clin Immunol 2014; 133(6): 1676-85 e5
Walker JA, Barlow JL, McKenzie AN. Innate lymphoid cells--how did we miss them? Nat Rev Immunol 2013; 13(2): 75-87.
Mela CM, Steel A, Lindsay J, Gazzard BG, Gotch FM, Goodier MR. Depletion of natural killer cells in the colonic lamina propria of viraemic HIV-1-infected individuals. AIDS 2007; 21(16): 2177-82.
Taborda NA, Gonzalez SM, Alvarez CM, Correa LA, Montoya CJ, Rugeles MT. Higher frequency of NK and CD4+ T-cells in mucosa and potent cytotoxic response in HIV controllers. PLoS One 2015; 10(8): e0136292.
Sips M, Sciaranghella G, Diefenbach T, et al. Altered distribution of mucosal NK cells during HIV infection. Mucosal Immunol 2012; 5(1): 30-40.
Hong HS, Rajakumar PA, Billingsley JM, Reeves RK, Johnson RP. No monkey business: Why studying NK cells in non-human primates pays off. Front Immunol 2013; 4: 32.
Webster RL, Johnson RP. Delineation of multiple subpopulations of natural killer cells in rhesus macaques. Immunology 2005; 115(2): 206-14.
Reeves RK, Evans TI, Gillis J, Johnson RP. Simian immunodeficiency virus infection induces expansion of alpha4beta7+ and cytotoxic CD56+ NK cells. J Virol 2010; 84(17): 8959-63.
Reeves RK, Rajakumar PA, Evans TI, et al. Gut inflammation and indoleamine deoxygenase inhibit IL-17 production and promote cytotoxic potential in NKp44+ mucosal NK cells during SIV infection. Blood 2011; 118(12): 3321-30.
Li H, Richert-Spuhler LE, Evans TI, et al. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection. PLoS Pathog 2014; 10(12): e1004551.
Liyanage NP, Gordon SN, Doster MN, et al. Antiretroviral therapy partly reverses the systemic and mucosal distribution of NK cell subsets that is altered by SIVmac(2)(5)(1) infection of macaques. Virology 2014; 450-451: 359-68.
Evans TI, Li H, Schafer JL, et al. SIV-induced translocation of bacterial products in the liver mobilizes myeloid dendritic and natural killer cells associated with liver damage. J Infect Dis 2016; 213(3): 361-9.
Fuchs A, Vermi W, Lee JS, et al. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFNɣ-producing cells. Immunity 2013; 38(4): 769-81.
Fuchs A, Colonna M. Innate lymphoid cells in homeostasis, infection, chronic inflammation and tumors of the gastrointestinal tract. Curr Opin Gastroenterol 2013; 29(6): 581-7.
Mjosberg J, Bernink J, Golebski K, et al. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 2012; 37(4): 649-59.
Nussbaum JC, Van Dyken SJ, von Moltke J, et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 2013; 502(7470): 245-8.
Serafini N, Vosshenrich CA, Di Santo JP. Transcriptional regulation of innate lymphoid cell fate. Nat Rev Immunol 2015; 15(7): 415-28.
Hepworth MR, Monticelli LA, Fung TC, et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 2013; 498(7452): 113-7.
Magri G, Miyajima M, Bascones S, et al. Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat Immunol 2014; 15(4): 354-64.
Qiu J, Guo X, Chen ZM, et al. Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation through aryl hydrocarbon receptor signaling and regulation of microflora. Immunity 2013; 39(2): 386-99.
van de Pavert SA, Ferreira M, Domingues RG, et al. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity. Nature 2014; 508(7494): 123-7.
Mudd JC, Brenchley JM. ILC you later: Early and irreparable loss of innate lymphocytes in HIV infection. Immunity 2016; 44(2): 216-8.
Xu H, Wang X, Lackner AA, Veazey RS. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques. FASEB J 2015; 29(12): 5072-80.
Xu H, Wang X, Liu DX, Moroney-Rasmussen T, Lackner AA, Veazey RS. IL-17-producing innate lymphoid cells are restricted to mucosal tissues and are depleted in SIV-infected macaques. Mucosal Immunol 2012; 5(6): 658-69.
Zhang Z, Cheng L, Zhao J, et al. Plasmacytoid dendritic cells promote HIV-1-induced group 3 innate lymphoid cell depletion. J Clin Invest 2015; 125(9): 3692-703.
Kloverpris HN, Kazer SW, Mjosberg J, et al. Innate lymphoid cells are depleted irreversibly during acute HIV-1 infection in the absence of viral suppression. Immunity 2016; 44(2): 391-405.
Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol 2007; 25: 297-336.
Sandberg JK, Ljunggren HG. Development and function of CD1d-restricted NKT cells: Influence of sphingolipids, SAP and sex. Trends Immunol 2005; 26(7): 347-9.
Sandberg JK, Fast NM, Palacios EH, et al. Selective loss of innate CD4(+) V alpha 24 natural killer T cells in human immunodeficiency virus infection. J Virol 2002; 76(15): 7528-34.
Motsinger A, Haas DW, Stanic AK, Van Kaer L, Joyce S, Unutmaz D. CD1d-restricted human natural killer T cells are highly susceptible to human immunodeficiency virus 1 infection. J Exp Med 2002; 195(7): 869-79.
van der Vliet HJ, von Blomberg BM, Hazenberg MD, et al. Selective decrease in circulating V alpha 24+V beta 11+ NKT cells during HIV type 1 infection. J Immunol 2002; 168(3): 1490-5.
Moll M, Snyder-Cappione J, Spotts G, Hecht FM, Sandberg JK, Nixon DF. Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2. Blood 2006; 107(8): 3081-3.
Yang OO, Wilson SB, Hultin LE, et al. Delayed reconstitution of CD4+ iNKT cells after effective HIV type 1 therapy. AIDS Res Hum Retroviruses 2007; 23(7): 913-22.
Moll M, Kuylenstierna C, Gonzalez VD, et al. Severe functional impairment and elevated PD-1 expression in CD1d-restricted NKT cells retained during chronic HIV-1 infection. Eur J Immunol 2009; 39(3): 902-11.
Moll M, Andersson SK, Smed-Sorensen A, Sandberg JK. Inhibition of lipid antigen presentation in dendritic cells by HIV-1 Vpu interference with CD1d recycling from endosomal compartments. Blood 2010; 116(11): 1876-84.
Ibarrondo FJ, Wilson SB, Hultin LE, et al. Preferential depletion of gut CD4-expressing iNKT cells contributes to systemic immune activation in HIV-1 infection. Mucosal Immunol 2013; 6(3): 591-600.
Leeansyah E, Ganesh A, Quigley MF, et al. Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood 2013; 121(7): 1124-35.
Kjer-Nielsen L, Patel O, Corbett AJ, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 2012; 491(7426): 717-23.
Cosgrove C, Ussher JE, Rauch A, et al. Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection. Blood 2013; 121(6): 951-61.
Fernandez CS, Amarasena T, Kelleher AD, et al. MAIT cells are depleted early but retain functional cytokine expression in HIV infection. Immunol Cell Biol 2015; 93(2): 177-88.
Eberhard JM, Hartjen P, Kummer S, et al. CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression. PLoS One 2014; 9(11): e111323.
Khaitan A, Kilberg M, Kravietz A, et al. HIV-infected children have lower frequencies of CD8+ Mucosal-Associated Invariant T (MAIT) cells that correlate with innate, Th17 and Th22 cell subsets. PLoS One 2016; 11(8): e0161786.
Leeansyah E, Svard J, Dias J, et al. Arming of MAIT cell cytolytic antimicrobial activity is induced by IL-7 and defective in HIV-1 infection. PLoS Pathog 2015; 11(8): e1005072.
Sandberg JK, Dias J, Shacklett BL, Leeansyah E. Will loss of your MAITs weaken your HAART?[corrected] AIDS 2013; 27(16): 2501-4. .
Greathead L, Metcalf R, Gazzard B, Gotch F, Steel A, Kelleher P. CD8+/CD161++ mucosal-associated invariant T-cell levels in the colon are restored on long-term antiretroviral therapy and correlate with CD8+ T-cell immune activation. AIDS 2014; 28(11): 1690-2.
Vinton C, Wu F, Rossjohn J, et al. Mucosa-associated invariant T cells are systemically depleted in simian immunodeficiency virus-infected rhesus macaques. J Virol 2016; 90(9): 4520-9.
Brandtzaeg P, Bosnes V, Halstensen TS, Scott H, Sollid LM, Valnes KN. T lymphocytes in human gut epithelium preferentially express the alpha/beta antigen receptor and are often CD45/UCHL1-positive. Scand J Immunol 1989; 30(1): 123-8.
Nilssen DE, Muller F, Oktedalen O, et al. Intraepithelial gamma/delta T cells in duodenal mucosa are related to the immune state and survival time in AIDS. J Virol 1996; 70(6): 3545-50.
Kagnoff MF. Current concepts in mucosal immunity. III. Ontogeny and function of gamma delta T cells in the intestine. Am J Physiol 1998; 274(3 Pt 1): G455-8.
Bonneville M, O’Brien RL, Born WK. Gammadelta T cell effector functions: A blend of innate programming and acquired plasticity. Nat Rev Immunol 2010; 10(7): 467-78.
Li H, Pauza CD. HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative gammadelta T cells which are lost during progression to AIDS. Blood 2011; 118(22): 5824-31.
Groh V, Steinle A, Bauer S, Spies T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 1998; 279(5357): 1737-40.
Sciammas R, Bluestone JA. TCRgammadelta cells and viruses. Microbes Infect Inst Pasteur 1999; 1(3): 203-12.
Nilssen DE, Brandtzaeg P. Intraepithelial ɣδ T cells remain increased in the duodenum of AIDS patients despite antiretroviral treatment. PLoS One 2012; 7(1): e29066.
Poles MA, Barsoum S, Yu W, et al. Human immunodeficiency virus type 1 induces persistent changes in mucosal and blood gammadelta T cells despite suppressive therapy. J Virol 2003; 77(19): 10456-67.
Kosub DA, Lehrman G, Milush JM, et al. Gamma/Delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections. J Virol 2008; 82(3): 1155-65.
Harris LD, Klatt NR, Vinton C, et al. Mechanisms underlying gammadelta T-cell subset perturbations in SIV-infected Asian rhesus macaques. Blood 2010; 116(20): 4148-57.
Soriano-Sarabia N, Archin NM, Bateson R, et al. Peripheral Vγ9Vδ2T cells are a novel reservoir of latent HIV infection. PLoS Pathog 2015; 11(10): e1005201.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy