Vδ1 Effector and Vδ2 γδ T-Cell Subsets Shift in Frequency and Are Linked to Plasma Inflammatory Markers During Antiretroviral Therapy-Suppressed HIV Infection

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(+) gamma delta T cells. Methods To elucidate gamma delta 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 gamma delta T-cell subset frequencies. Results Thirty-nine distinct gamma delta T-cell subsets were identified (22 V delta 1(+), 14 V delta 2(+), and 3 V delta 1(-)V delta 2(-)V gamma 9(+)) and TIGIT was nearly exclusively found on the V delta 1(+)CD45RA(+)CD27(-) effector populations. People with ART-suppressed HIV infection (PWH) exhibited high frequencies of distinct clusters of V delta 1(+) effectors distinguished via CD8, CD16, and CD38 expression. Among V delta 2(+) cells, most V gamma 9(+) (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' V delta 1(+)CD45RA(+)CD27(+) cells in older individuals, regardless of HIV status. Plasma inflammatory markers were selectively linked to subsets of V delta 1(+) and V delta 2(+) cells. Conclusions These results further elucidate gamma delta T-cell subset complexity and reveal distinct alterations and connections with inflammatory pathways of V delta 1(+) effector and V delta 2(+) innate-like subsets during ART-suppressed HIV infection.