Adhesion molecules and kinases involved in gamma delta T cells migratory pathways: Implications for viral and autoimmune diseases

gamma delta 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 V delta 1 and V delta 2 gamma delta T 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-gamma-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 V delta 1 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 V delta 2 gamma delta T cells and this is related to interleukin-12-mediated upregulation of NKRP1A. Finally, the possible role of gamma delta T lymphocytes in post-transplantation immune reconstitution is discussed.