Jennifer E Snyder-Cappione

Background Chronic inflammation is prevalent with antiretroviral therapy (ART)-suppressed human immunodeficiency virus (HIV) infection and one immune cell subset putatively driving this phenomenon is TIGIT+ γδ T cells. Methods To elucidate γδ T-cell phenotypic diversity, spectral flow cytometry was performed on blood lymphocytes from individuals of a HIV and aging cohort and data were analyzed using bioinformatic platforms. Plasma inflammatory markers were measured and correlated with γδ T-cell subset frequencies. Results Thirty-nine distinct γδ T-cell subsets were identified (22 Vδ1+, 14 Vδ2+, and 3 Vδ1−Vδ2−Vγ9+) and TIGIT was nearly exclusively found on the Vδ1+CD45RA+CD27− effector populations. People with ART-suppressed HIV infection (PWH) exhibited high frequencies of distinct clusters of Vδ1+ effectors distinguished via CD8, CD16, and CD38 expression. Among Vδ2+ cells, most Vγ9+ (innate-like) clusters were lower in PWH; however, CD27+ subsets were similar in frequency between participants with and without HIV. Comparisons by age revealed lower ‘naive’ Vδ1+CD45RA+CD27+ cells in older individuals, regardless of HIV status. Plasma inflammatory markers were selectively linked to subsets of Vδ1+ and Vδ2+ cells. Conclusions These results further elucidate γδ T-cell subset complexity and reveal distinct alterations and connections with inflammatory pathways of Vδ1+ effector and Vδ2+ innate-like subsets during ART-suppressed HIV infection.