Department of Pathology, Oslo University Hospital and University of Oslo, Oslo, Norway.
Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Mucosal Immunol. 2021 Mar;14(2):402-410. doi: 10.1038/s41385-020-0315-5. Epub 2020 Jun 22.
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 cells expressed CD69 and CD161, but only a minor fraction expressed CD103. Functionally, intestinal CD4 T cells were very potent cytokine producers; the vast majority being polyfunctional T1 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.
在小鼠和人类中的研究表明，非淋巴组织中的 CD8 T 细胞免疫监视主要由常驻群体主导。CD4 T 细胞是否使用相同的策略来监测外周组织尚不清楚。在这里，我们研究了人类移植十二指肠中 CD4 T 细胞的更新，结果表明，在移植后一年，大多数 CD4 T 细胞仍然是供体来源的。与外周血中的记忆 CD4 T 细胞不同，肠道 CD4 T 细胞表达 CD69 和 CD161，但只有一小部分表达 CD103。功能上，肠道 CD4 T 细胞是非常有效的细胞因子产生细胞；绝大多数是多功能 T1 细胞，而一小部分产生 IL-17。有趣的是，一部分肠道 CD4 T 细胞在激活后产生颗粒酶 B 和穿孔素。总之，我们表明肠道 CD4 T 细胞区室主要由常驻群体主导，这些群体可存活超过 1 年。这一发现对于开发口服疫苗和治疗肠道疾病具有重要意义。
