Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
*HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Key Clinical Department of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China; and
†AIDS Institute and Department of Microbiology, Research Center for Infection and Immunity, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Correspondence to: Zhiwei Chen, PhD, AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong, China (e-mail: firstname.lastname@example.org).
The first two authors contributed equally to this paper.
Supported by the National Mega Project on the prevention and treatment of AIDS (2012ZX10001006-001-009 to H.W. and Q.P., 2008ZX10001-006 to H.W. and 2012ZX10001009-001-001 to Z.C.), Hong Kong AIDS Trust Fund (MSS183R to Z.C.), and the HKU-UDF and LKS Faculty of Medicine Matching Fund for financial supports to the HKU-AIDS Institute.
The authors have no funding or conflicts of interest to disclose.
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Received December 11, 2012
Accepted March 19, 2013