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⁺ 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. [ABSTRACT FROM AUTHOR]