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Preferential loss of gut-homing ?4?7 CD4⁺ T cells and their circulating functional subsets in acute HIV-1 infection.

ABSTRACT: Preferential infection and depletion of gut-homing ?4?7 CD4⁺ T cells in the blood are observed in chronic HIV/SIV infection. The dynamic change in gut-homing ?4?7 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 ?4?7 CD4⁺ T cells and their functional subsets. We examined the frequency, absolute number, and functionality of gut-homing ?4?7 CD4⁺ T cells in 26 acute HIV-1-infected patients compared with 20 healthy individuals. We found that circulating gut-homing ?4?7 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 ?4?7 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.

SUBMITTER: Lu X

PROVIDER: S-EPMC5101442 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Preferential loss of gut-homing α4β7 CD4+ T cells and their circulating functional subsets in acute HIV-1 infection.

Lu Xiaofan X Li Zhen Z Li Qunhui Q Jiao Yanmei Y Ji Yunxia Y Zhang Hongwei H Liu Zhuoming Z Li Wei W Wu Hao H

Cellular & molecular immunology 20150817 6

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, abs ...[more]

PMID: 26277899

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Project description:Latent HIV infection is the main barrier to cure, and most HIV-infected cells reside in the gut, where distinct but unknown mechanisms may promote viral latency. Transforming growth factor β (TGF-β), which induces the expression of CD103 on tissue-resident memory T cells, has been implicated in HIV latency. Using CD103 as a surrogate marker to identify cells that have undergone TGF-β signaling, we compared the HIV RNA/DNA contents and cellular transcriptomes of CD103+ and CD103- CD4 T cells from the blood and rectum of HIV-negative (HIV-) and antiretroviral therapy (ART)-suppressed HIV-positive (HIV+) individuals. Like gut CD4+ T cells, circulating CD103+ cells harbored more HIV DNA than did CD103- cells but transcribed less HIV RNA per provirus. Circulating CD103+ cells also shared a gene expression profile that is closer to that of gut CD4 T cells than to that of circulating CD103- cells, with significantly lower expression levels of ribosomal proteins and transcriptional and translational pathways associated with HIV expression but higher expression levels of a subset of genes implicated in suppressing HIV transcription. These findings suggest that blood CD103+ CD4 T cells can serve as a model to study the molecular mechanisms of HIV latency in the gut and reveal new cellular factors that may contribute to HIV latency.IMPORTANCE The ability of HIV to establish a reversibly silent, "latent" infection is widely regarded as the main barrier to curing HIV. Most HIV-infected cells reside in tissues such as the gut, but it is unclear what mechanisms maintain HIV latency in the blood or gut. We found that circulating CD103+ CD4+ T cells are enriched for HIV-infected cells in a latent-like state. Using RNA sequencing (RNA-seq), we found that CD103+ T cells share a cellular transcriptome that more closely resembles that of CD4+ T cells from the gut, suggesting that they are homing to or from the gut. We also identified the cellular genes whose expression distinguishes gut CD4+ or circulating CD103+ T cells from circulating CD103- T cells, including some genes that have been implicated in HIV expression. These genes may contribute to latent HIV infection in the gut and may serve as new targets for therapies aimed at curing HIV.

Dataset Information

Preferential loss of gut-homing ?4?7 CD4⁺ T cells and their circulating functional subsets in acute HIV-1 infection.

Publications

Preferential loss of gut-homing α4β7 CD4<sup>+</sup> T cells and their circulating functional subsets in acute HIV-1 infection.

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Dataset Information

Preferential loss of gut-homing ?4?7 CD4+ T cells and their circulating functional subsets in acute HIV-1 infection.

Publications

Preferential loss of gut-homing α4β7 CD4<sup>+</sup> T cells and their circulating functional subsets in acute HIV-1 infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Preferential loss of gut-homing ?4?7 CD4⁺ T cells and their circulating functional subsets in acute HIV-1 infection.