Failure of γδ T Cell Recovery in the Gut With Effective Anti-HIV Therapy

Infection with HIV alters γδ T cells, and while these changes have been well documented in blood, they are less well understood in the gut.

Phenotype (specifically HIV coreceptor expression) and polyfunctionality, as defined by concomitant cytokine expression, were evaluated in γδ T cells in the blood and gut of effectively treated people living with HIV (PLWH) and people without HIV (PWOH). Mononuclear cells were isolated from blood and recto-sigmoid colon biopsy tissue, and γδ T cells were evaluated by flow cytometry.

The expression of α4β7 was significantly higher in gut-derived γδ T cells of PLWH compared to PWOH and blood-derived cells of both groups. The polyfunctionality profile of gut-derived γδ T cells in PLWH was also different than that of PWOH, with significantly higher expression of IFN-γ in the gut-derived cells.

The alterations observed in gut-derived γδ T cells from effectively treated PLWH suggest cellular function is not restored with prolonged antiretroviral therapy (ART) and may contribute to a chronic inflammatory state. Trial Registration: HAVARTI trial registration (ClinicalTrials.gov): NCT03147859.