Vδ1+ and Vδ2+ gamma delta T cell subsets exert distinct functional profiles with aviremic HIV infection and aging

Abstract

Abstract Populations of gamma delta T cells exert different effector function profiles (inflammatory (Th1/Th17) vs. immunoregulatory (Th2/Treg)) in response to non-antigen specific signals in a microenvironment. The nature of gamma delta T cell lineage commitment versus functional capacity at the single cell level is unclear. Also, gamma delta T cells are implicated as drivers of the chronic inflammation found with normal aging and ART-suppressed HIV infection; however, the precise subsets involved in this phenomenon are currently unknown. To address these questions, we optimized a 31-color Intracellular Cytokine Staining (ICS) panel enabling measurement of 10 cytokines, as well as Ki67, granzyme B, and CD107a for use with PBMC from participants of a HIV and Aging cohort. Multi-variate analysis (opt-SNE) of the collected dataset revealed striking differences in the overall functional potential of the V delta 1 (Vδ1) and V delta 2 (Vδ2) subsets, with many Vδ1+ cells not producing any of the cytokines measured. Distinct differences of both the Vδ1+ and Vδ2+ subsets were found between the HIV infected and age-stratified subject groups. Individual gamma delta T cells with a ‘Th0’ phenotype, producing both Th1 and Th2 lineage cytokines, were present in both Vδ1+ and Vδ2+ subsets. Also, HIV+ subjects lacked Vδ2+ cells expressing CD107a, indicating a specific defect in the cytotoxic function of this subset with HIV infection. Further investigation of gamma delta T cell functions and phenotypes could provide new insight into the biology of this unique T cell population and reveal novel therapeutic targets. Supported by a grant from NIH (R01AG060890-01)