HIV-1 shedding from the female genital tract is associated with increased Th1 cytokines/chemokines that maintain tissue homeostasis and proportions of CD8+FOXP3+ T cells.
HIV-1 shedding from the female genital tract is associated with increased Th1 cytokines/chemokines that maintain tissue homeostasis and proportions of CD8+FOXP3+ T cells.
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DOI：
10.1097/qai.0000000000000336
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发表时间：
2014-12-01
期刊：
影响因子：
--
通讯作者：
Hitti JE
中科院分区：
文献类型：
--
作者：
Bull ME;Legard J;Tapia K;Sorensen B;Cohn SE;Garcia R;Holte SE;Coombs RW;Hitti JE
HIV-1 shedding from the female genital tract is associated with increased sexual and perinatal transmission, and has been broadly evaluated in cross-sectional studies. However, few longitudinal studies have evaluated how the immune microenvironment effects shedding. Thirty-nine HIV-1–infected women had blood, cervicovaginal lavage (CVL), and biopsies of the uterine cervix taken quarterly for up to five years. Cytokines/chemokines were quantified by Luminex assay in CVL and cellular phenotypes were characterized using immunohistochemistry in cervical biopsies. Comparisons of cytokine/chemokine concentrations and the percent of tissue staining positive for T cells were compared using generalized estimating equations between non-shedding and shedding visits across all women, and within a subgroup of women who intermittently shed HIV-1. Genital HIV-1 shedding was more common when plasma HIV-1 was detected. Cytokines associated with cell growth (IL-7), Th1 cells/inflammation (IL-12p70), and fractalkine were significantly increased at shedding visits compared to non-shedding visits within intermittent shedders and across all subjects. Within intermittent shedders and across all subjects FOXP3+ T cells were significantly decreased at shedding visits. However, there were significant increases in CD8+ cells and proportions of CD8+FOXP3+ T cells associated with HIV-1 shedding. Within intermittent HIV-1 shedders, decreases in FOXP3+ T cells at the shedding visit suggests that local HIV-1 replication leads to CD4 T cell depletion, with increases in the proportion of CD8+FOXP3+ cells. HIV-1–infected cell loss may promote a cytokine milieu that maintains cellular homeostasis and increases immune suppressor cells in response to HIV-1 replication in the cervical tissues.
