Imbalances of Gut-Homing CD4+ T-Cell Subsets in HIV-1–Infected Chinese Patients

Abstract

Full reconstitution of CD4 T cells in both peripheral blood and mucosal tissues is a desirable goal of treating AIDS patients. To date, few studies have investigated the potential role of gut-homing CD4 T-cell subsets as biomarkers in assisting Asian populations infected with HIV-1. A large cross-sectional study was conducted among Chinese patients with focus on the frequency, absolute number, and ratio of gut-homing Th1, Th17, and Treg subsets in 3 groups of age- and gender-matched study subjects: healthy donors, untreated AIDS patients, and antiretroviral therapy (ART)-treated patients with sustained undetectable viral load. HIV-1 chronic infection resulted in positively correlated loss of total and gut-homing CD4 T cells (P < 0.001) among patients compared with healthy controls. Profiles of T-cell subsets, however, were different between total and gut-homing CD4 T cells in terms of frequency and absolute number. ART partially restored the frequencies of gut-homing Th1, Th17, and Treg cells but the lost number of gut-homing Th17 cells was found not easily reversible. These changes together with an increased frequency of gut-homing CD4 Treg cells led to dual imbalances of gut-homing Th1/Treg and Th17/Treg ratios, which were negatively correlated with viral load (P = 0.014 and P < 0.001) and hardly restored even by prolonged ART. Our findings provide new insights into the investigation of gut-homing Th1/Treg and Th17/Treg imbalances in AIDS patients, which may have potential implications on the reconstitution of mucosal CD4 T cells.