Preferential loss of gut-homing α4β7 CD4+T cells and their circulating functional subsets in acute HIV-1 infection.
Preferential infection and depletion of gut-homing α4β7 CD4+T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing α4β7 CD4+T cells and their functional subsets during the acute stages of HIV-1 infection are less documented. Therefore, we conducted a cohort study to investigate whether acute HIV-1 infection induced abnormalities in gut-homing α4β7 CD4+T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing α4β7 CD4+T cells in 26 acute HIV-1-infected patients compared with 20 healthy individuals. We found that circulating gut-homing α4β7 CD4+T cells were preferentially depleted during acute HIV-1 infection and were positively correlated with absolute CD4+T-cell count in blood. Notably, Th17 and Th1 cell subsets of gut-homing CD4+T cells were also decreased, which resulted in an imbalance of T helper cells (Th1):regulatory T cells (Treg) and Treg:Th17 ratios. Gut-homing Th17 and Th1 cells were also positively correlated with the absolute number of total CD4+T cells and gut-homing CD4+T cells. The gut-homing Treg:Th17 ratio was inversely correlated with the CD4+T-cell count. Taken together, the analyses of our acute HIV-1 cohort demonstrate that gut-homing α4β7 CD4+T cells and their functional subsets were profoundly depleted during acute HIV-1 infection, which may have resulted in the persistent loss of circulating CD4+T cells and an imbalance of Th1:Treg and Treg:Th17 ratios and contribute to HIV-1 disease pathogenesis.
STD/HIV Research Laboratory, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.|Beijing Key Laboratory for HIV/AIDS Research, Beijing 100069, People's Republic of China.
Xiaofan
X
Lu
STD/HIV Research Laboratory, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.|Beijing Key Laboratory for HIV/AIDS Research, Beijing 100069, People's Republic of China.
Zhen
Z
Li
Center for Infectious Diseases, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.
Qunhui
Q
Li
STD/HIV Research Laboratory, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.|Beijing Key Laboratory for HIV/AIDS Research, Beijing 100069, People's Republic of China.
Yanmei
Y
Jiao
STD/HIV Research Laboratory, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.|Beijing Key Laboratory for HIV/AIDS Research, Beijing 100069, People's Republic of China.
Yunxia
Y
Ji
Center for Infectious Diseases, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.
Hongwei
H
Zhang
Case Comprehensive Cancer Center and Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Zhuoming
Z
Liu
STD/HIV Research Laboratory, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.|Beijing Key Laboratory for HIV/AIDS Research, Beijing 100069, People's Republic of China.|Center for Infectious Diseases, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.
Wei
W
Li
Center for Infectious Diseases, Beijing You-An Hospital, Capital Medical University, Beijing 100069, People's Republic of China.
Hao
H
Wu
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D055815:Young Adult
D016023:Integrins; C071777:integrin alpha4beta7