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

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: alpha 4 beta 7 integrin (α4β7); cytokine polyfunctionality; human immunodeficiency virus (HIV); recto-sigmoid colon biopsy; γδ T cells.