Distinct subsets of Vδ1 effector and Vδ2 γδ T cells shift in frequency and are linked to plasma inflammatory markers during ART-suppressed HIV infection

Chronic inflammation is prevalent with ART-suppressed HIV-infection and one immune cell subset putatively driving this phenomenon is TIGIT + γδ T cells.To elucidate γδ T cell phenotypic diversity, spectral flow cytometry was performed on blood lymphocytes from individuals of an HIV and Aging cohort and data were analyzed using bioinformatic platforms. Plasma inflammatory markers were measured and correlated with γδ T cell subset frequencies.39 distinct γδ T cell subsets were identified (22 Vδ1+, 14 Vδ2+, and three Vδ1-Vδ2-Vγ9+) and TIGIT was nearly exclusively found on the Vδ1+ CD45RA+ CD27- 'effector' populations. People living with ART-suppressed HIV-infection (PLWH) exhibited high frequencies of distinct clusters of Vδ1+ effectors distinguished via CD8, CD56, CD16, and CD38 expression. Among Vδ2+ cells, most Vγ9+ ('innate-effector') clusters were lower in PLWH, yet CD27+ subsets were similar in frequency between participants with and without HIV. Comparisons by age revealed lower 'naïve' Vδ1 + CD45RA+ CD27+ in older individuals, regardless of HIV status. Plasma inflammatory markers were selectively linked to subsets of Vδ1+ and Vδ2+ cells.These results further elucidate γδ T cell subset complexity and reveal distinct alterations and connections with inflammatory pathways of Vδ1+ effector and Vδ2+ innate-effector subsets with ART-suppressed HIV infection.