Mucosal Immunology ( IF 8 ) Pub Date : 2020-06-22 , DOI: 10.1038/s41385-020-0315-5 Raquel Bartolomé-Casado 1 , Ole J B Landsverk 1 , Sudhir Kumar Chauhan 1, 2 , Frank Sætre 1 , Kjersti Thorvaldsen Hagen 1 , Sheraz Yaqub 3 , Ole Øyen 4 , Rune Horneland 4 , Einar Martin Aandahl 2, 4 , Lars Aabakken 5 , Espen S Bækkevold 1 , Frode L Jahnsen 1
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+ TRM cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4+ TRM cells were very potent cytokine producers; the vast majority being polyfunctional TH1 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.
中文翻译:
CD4+ T 细胞在人类小肠中持续存在多年,并显示出 TH1 细胞因子谱。
对小鼠和人类的研究表明,非淋巴组织中的CD8 + T 细胞免疫监视由常驻人群主导。CD4 + T 细胞是否使用相同的策略来调查外周组织尚不清楚。在这里,检查人体移植十二指肠中 CD4 + T 细胞的周转率,我们证明大多数 CD4 + T 细胞在移植一年后仍来自供体。与外周血中的记忆 CD4 + T 细胞相反,肠道 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细胞是非常有效的细胞因子生产者;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 细胞在激活后会产生颗粒酶 B 和穿孔素。我们一起表明,肠道 CD4 + T 细胞区室由存活超过 1 年的常住种群主导。这一发现与开发口服疫苗和治疗肠道疾病具有高度相关性。