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比较 HIV 感染和溃疡性结肠炎中记忆 T 细胞亚群的整合素 α4β7 表达模式。

Comparison of the integrin α4β7 expression pattern of memory T cell subsets in HIV infection and ulcerative colitis.

机构信息

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Infectious Disease Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

PLoS One. 2019 Jul 29;14(7):e0220008. doi: 10.1371/journal.pone.0220008. eCollection 2019.

Abstract

Anti-α4β7 therapy with vedolizumab (VDZ) has been suggested as possible immune intervention in HIV. Relatively little is known about the α4β7-integrin (α4β7) expression of different T-cell subsets in different anatomical compartments of healthy individuals, patients with HIV or inflammatory bowel disease (IBD). Surface expression of α4β7 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 α4β7 on total CD4+ T cells were detectable regardless of the disease status or (VDZ) treatment status in peripheral blood and the studied tissues. Peripheral α4β7+ CD4+ T cells of healthy individuals and patients with UC showed a higher activation status and were more frequently CCR5+ than their α4β7- counterparts. Also, the frequency of α4β7+ 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 naïve α4β7+ CD4+ T cells was significantly reduced under VDZ treatment. The results of the current study will contribute to the understanding of the dynamics of α4β7 expression pattern on T cells in HIV and UC and will be useful for future studies investigating VDZ as possible HIV cure strategy.

摘要

使用 vedolizumab (VDZ) 抑制 α4β7 治疗已被提议作为 HIV 的一种潜在免疫干预措施。目前,对于健康个体、HIV 感染者或炎症性肠病 (IBD) 患者不同解剖部位不同 T 细胞亚群的 α4β7 整合素 (α4β7) 表达情况,我们了解甚少。通过多色流式细胞术,我们评估了健康志愿者(n=15)、HIV 感染者(n=52)和溃疡性结肠炎 (UC) 患者(n=14,其中 6 名接受 vedolizumab 治疗)外周血中 T 细胞的 α4β7 表面表达和激活、归巢及耗竭标志物的频率,此外还分析了淋巴结细胞(n=6)、健康志愿者的肠道衍生细胞(n=5)和 UC 患者(n=6)的细胞。我们还对一名接受 vedolizumab 治疗合并 UC 的 HIV 患者进行了 PBMC 纵向样本研究。总的来说,无论疾病状态或(VDZ)治疗状态如何,在外周血和研究组织中,我们都只能检测到总 CD4+T 细胞上 α4β7 频率的微小变化。与健康个体和 UC 患者的 α4β7- CD4+T 细胞相比,外周 α4β7+CD4+T 细胞具有更高的激活状态,并且更频繁地表达 CCR5+。此外,与健康个体相比,HIV 感染者外周血 CD4+效应记忆 T 细胞中 α4β7+细胞的频率显著降低,而在接受 ART 治疗的 HIV 患者中,这种降低的频率并未恢复。相反,在 vedolizumab 治疗下,外周血幼稚的 α4β7+CD4+T 细胞的频率显著降低。本研究的结果将有助于理解 HIV 和 UC 中 T 细胞上 α4β7 表达模式的动态变化,并将有助于未来研究 vedolizumab 作为 HIV 治愈策略的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71a0/6663001/e297472233fb/pone.0220008.g001.jpg

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