CD4+T cells persist for years in the human small intestine and display a TH1 cytokine profile
CD4+T cells persist for years in the human small intestine and display a TH1 cytokine profile
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DOI：
10.1038/s41385-020-0315-5
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发表时间：
2020-06-22
影响因子：
8
通讯作者：
Jahnsen, Frode L.
中科院分区：
文献类型：
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作者：
Bartolome-Casado, Raquel;Landsverk, Ole J. B.;Jahnsen, Frode L.
对小鼠和人类的研究表明，非淋巴组织中的CD8(+)T细胞免疫监控主要由常住人口主导。CD4(+)T细胞是否使用相同的策略来检测周围组织还不太清楚。在这里，我们检测了人类移植十二指肠中的CD4(+)T细胞的周转情况，我们证明大多数的CD4(+)T细胞在移植一年后仍然是供者来源的。与外周血中记忆的CD4(+)T细胞相比，肠道的CD4(+)T(RM)细胞表达CD69和CD161，但只有一小部分表达CD103。在功能上，肠道CD4(+)T(RM)细胞是非常强大的细胞因子产生细胞；绝大多数是多功能T(H)1细胞，而一小部分产生IL-17。有趣的是，一小部分肠道CD4(+)T细胞激活后产生颗粒酶-B和穿孔素。总而言之，我们发现肠道中的CD4(+)T细胞由存活1年以上的常住人口主导。这一发现对于开发口服疫苗和肠道疾病的治疗方法具有很高的相关性。
Studies in mice and humans have shown that CD8(+)T cell immunosurveillance in non-lymphoid tissues is dominated by resident populations. Whether CD4(+)T cells use the same strategies to survey peripheral tissues is less clear. Here, examining the turnover of CD4(+)T cells in transplanted duodenum in humans, we demonstrate that the majority of CD4(+)T cells were still donor-derived one year after transplantation. In contrast to memory CD4(+)T cells in peripheral blood, intestinal CD4(+)T(RM)cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4(+)T(RM)cells were very potent cytokine producers; the vast majority being polyfunctional T(H)1 cells, whereas a minor fraction produced IL-17. Interestingly, a fraction of intestinal CD4(+)T cells produced granzyme-B and perforin after activation. Together, we show that the intestinal CD4(+)T-cell compartment is dominated by resident populations that survive for more than 1 year. This finding is of high relevance for the development of oral vaccines and therapies for diseases in the gut.