Abstract
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.
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Acknowledgements
This project was supported by the 12th Five-Year Mega Project of China on the prevention and treatment of AIDS, viral hepatitis and other infectious disease (2014ZX10001002-001-002, 2012ZX10001-006), the Beijing Municipal of Science and Technology Major Project (D141100000314005), and Beijing Natural Science Foundation (7132077). We also thank the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZY201401) and the Beijing Key Laboratory for HIV/AIDS Research (BZ0089) for financial support for this work.
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Lu, X., Li, Z., Li, Q. et al. Preferential loss of gut-homing α4β7 CD4+ T cells and their circulating functional subsets in acute HIV-1 infection. Cell Mol Immunol 13, 776–784 (2016). https://doi.org/10.1038/cmi.2015.60
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DOI: https://doi.org/10.1038/cmi.2015.60
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