Distortion of memory Vδ2 γδ T cells contributes to immune dysfunction in chronic HIV infection

gamma delta T cells play important roles in innate immunity as the first-line of defense against infectious diseases. Human immunodeficiency virus (HIV) infection disrupts the balance between V delta(1) T cells and V delta(2) T cells and causes dysfunction among gamma delta T cells. However, the biological mechanisms and clinical consequences of this disruption require further investigation. In this study, we performed a comprehensive analysis of phenotype and function of memory gamma delta T cells in cohorts of Chinese individuals with HIV infection. We found a dynamic change inmemory V delta(2) gamma delta T cells, skewed toward an activated and terminally differentiated effector memory phenotype T-EMRA V delta(2) gamma delta T cell, which may account for the dysfunction of V delta(2) gamma delta T cells in HIV disease. In addition, we found that IL-17-producing gamma delta T cells were significantly increased in HIV-infected patients with fast disease progression and positively correlated with HLA-DR+ gamma delta T cells and CD38(+) HLA-DR+ gamma delta T cells. This suggests the IL-17 signaling pathway is involved in gamma delta T-cell activation and HIV pathogenesis. Our findings provide novel insights into the role of V delta(2) T cells during HIV pathogenesis and represent a sound basis on which to consider immune therapies with these cells.