Vδ1+ and Vδ2+ gamma delta T cells express different marker signatures and are distinctly linked to plasma markers of inflammation with ART-suppressed HIV infection and normal aging

Abstract

Abstract Our previous work implicates γδ T cells as an inflammatory driver in ART-suppressed HIV infection and suggests that this unique T cell population serves distinct roles in the ‘inflamm-aging’ that occurs with and without virally controlled HIV. In this study, we honed our previous findings to determine the precise γδ T cell subsets that are driving inflammation with age +/− HIV infection. We performed in depth immunophenotyping of circulating γδ T cells via multi-color flow cytometry and analysis of plasma markers of inflammation, coagulation, and intestinal permeability from subjects of our HIV and Aging cohort, which includes ART-suppressed HIV+ individuals and matched uninfected controls stratified by age into younger (≤35yo) and older (≥50yo) groups. We found discrete differences in the combinational expression the inhibitory receptors (IRs) TIGIT, PD-1, and CD160 between the Vδ1+ and the Vδ2+ γδ T cell subsets with HIV infection and healthy aging. Also, we found that specific IR signatures of Vδ1+ and Vδ2+ γδ T cells correlated with plasma inflammatory markers; however, different connections between the plasma analytes were found for each of the two γδ T cell subsets. Taken together, these data indicate that Vδ1+ and Vδ2+ γδ T cells exist in distinct states and possess divergent roles in the ‘inflamm-aging’ found in aviremic HIV+ infection and with normal aging. Further investigation into the anatomical locations, ex vivo functions, and additional surface markers that define γδ T cell subsets may reveal novel therapeutic targets to abrogate the aberrant inflammation found with HIV infection, aging, and other inflammatory conditions.