CD8+ T-cell-mediated Non-cytolytic Suppression of Human Immunodeficiency Viruses

Author(s): C. Vella, R. S. Daniels.

Journal Name: Current Drug Targets - Infectious Disorders

Volume 3 , Issue 2 , 2003

Abstract:

Major Histocompatibility (MHC)-restricted Cytotoxic T-Lymphocytes (CTL) kill Human Immunodeficiency Virus (HIV)-infected cells. In addition, activated CD8+ T-lymphocytes from HIV-infected individuals suppress virus replication in vitro by producing antiviral factor (CAF). The effector mechanism(s) of CAF involves modulation of HIV gene transcription, is non-cytolytic and mediated in part by soluble antiviral factors. Initially, CAF activity was shown to be more vigorous in activated CD8+ cells and cell free supernatants (SNs) from asymptomatic individuals compared to those with AIDS, suggesting a protective role in vivo. CAF-mediated suppression is also evident in animal models of immunodeficiency virus infection. Several soluble molecules that contribute to non-cytolytic virus suppression have been characterised, including α- and β-chemokines and interleukin-16 (IL-16), but these are distinct from CAF. Two agents possessing certain CAF-like characteristics, modified antithrombin 111 (AT111) and the human a-defensins, have been described but their antiviral mechanisms are not fully understood. CAF-secretion may not be virus-specific as similar activity is found in activated CD8+ cells / SNs from humans and chimpanzees seronegative for HIV-1. Recent data indicates that the secretion of CAF is MHC-restricted and both cytolytic and non-cytolytic mechanisms are mediated by CTL. If the latter is correct, a single appropriate stimulus could be used to enhance both effector mechanisms in vivo. This paper reviews research aimed at characterising HIV-suppressive factors and raises other questions that must be considered for the development of prophylactic and therapeutic strategies leading to the safe and effective control of HIV.

Keywords: non-cytolytic suppression, hiv, caf, defensins, modified-at111, Il-16, chemokines

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Article Details

VOLUME: 3
ISSUE: 2
Year: 2003
Page: [97 - 113]
Pages: 17
DOI: 10.2174/1568005033481196
Price: $58