Comparison Of The Integrin A4 Ss 7 Expression Pattern Of Memory T Cell Subsets In Hiv Infection And Ulcerative Colitis
PLOS ONE(2019)
摘要
Anti-alpha 4 ss 7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the alpha 4 ss 7-integrin (alpha 4 ss 7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of alpha 4 ss 7 as well as the frequency of activation, homing and exhaustion markers of T cells were assessed by multicolour flow cytometry in healthy volunteers (n = 15) compared to HIV infected patients (n = 52) or patients diagnosed with ulcerative colitis (UC) (n = 14), 6 of whom treated with vedolizumab. In addition, lymph nodal cells (n = 6), gut-derived cells of healthy volunteers (n = 5) and patients with UC (n = 6) were analysed. Additionally, we studied longitudinal PBMC samples of an HIV patient who was treated with vedolizumab for concomitant UC. Overall, only minor variations of the frequency of alpha 4 ss 7 on total CD4(+) T cells were detectable regardless of the disease status or (VDZ) treatment status in peripheral blood and the studied tissues. Peripheral alpha 4 ss 7(+) CD4(+) T cells of healthy individuals and patients with UC showed a higher activation status and were more frequently CCR5(+) than their alpha 4 ss 7(-) counterparts. Also, the frequency of alpha 4 ss 7(+) cells was significantly lower in peripheral blood CD4(+) effector memory T cells of HIV-infected compared to healthy individuals and this reduced frequency did not recover in HIV patients on ART. Conversely, the frequency of peripheral blood naive alpha 4 ss 7(+) CD4(+) T cells was significantly reduced under VDZ treatment. The results of the current study will contribute to the understanding of the dynamics of alpha 4 ss 7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy.
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关键词
integrin,ulcerative colitis,hiv infection
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