Adhesion Molecules and Kinases Involved in γ δ T Cells Migratory Pathways:Implications for Viral and Autoimmune Diseases

Alessandro      Poggi; Silvia      Catellani; Daniela      Fenoglio; Giovanna      Borsellino; Luca      Battistini; Maria   Raffaella   Zocchi

Abstract

γ δ T lymphocytes are involved in the defence from viral and mycobacterial infections; however they are also responsible for autoimmune reactions. Herein, we discuss the characteristics of these cells, focusing on the mechanism(s) underlying extravasation and tissue localization. We show that Vδ1 and Vδ2 γ δT cells display differential expression of adhesion molecules and chemokine receptors, the former being preferentially PECAM-1+CXCR4+, the latter expressing NKRP1A and CXCR3. The two cell populations transmigrate across endothelial cells by activation of distinct kinase pathways and in response to interferon-γ-inducing protein-10 (IP-10/CXCL10) or stromal-derived factor-1 (SDF-1/CXCL12) according to the expression of the specific receptors CXCR3 and CXCR4. IP-10/CXCL10 and SDF-1/CXCL12-induced transmigration are phosphoinositide-3 kinase (PI-3K) and Akt/PKB-dependent. In addition, occupancy of CXCR3, but not of CXCR4, leads to CAMKII activation; blocking of CAMKII decreases IP-10/CXCL10 and 6Ckine/SLC/CCL21- driven transmigration. We report that HIV-1-infected patients have an increased number of circulating Vδ1 T cells possibly due to the interference of Tat protein on the function of chemokine receptors. In turn, patients with relapsing-remitting multiple sclerosis (MS), display an increase in peripheral Vδ2 γ δ T cells and this is related to interleukin-12-mediated upregulation of NKRP1A. Finally, the possible role of γ δ T lymphocytes in post-transplantation immune reconstitution is discussed.

Keywords: γ δ T lymphocytes, Multiple Sclerosis, HIV-1, Migration, CAMKII, PI-3K, NKRP1A, PECAM1