Guo Zijin, Jang Myoung Ho, Otani Kazuhiro, Bai Zhongbin, Umemoto Eiji, Matsumoto Masanori, Nishiyama Mika, Yamasaki Mikako, Ueha Satoshi, Matsushima Kouji, Hirata Takako, Miyasaka Masayuki
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Int Immunol. 2008 Mar;20(3):307-15. doi: 10.1093/intimm/dxm143. Epub 2008 Jan 9.
CD4(+)CD25(+) regulatory T cells (Tregs) have been implicated in the suppression of pathogenic responses to both self- and non-self-antigens in the intestine. However, their precise properties and functions in the gut, as well as the molecular basis of their recruitment to the gut, are poorly understood. Here, we found that most of the CD4(+)CD25(+) T cells in the small intestinal lamina propria (LP) express Foxp3 and exhibit an 'effector/memory' phenotype, CD44(hi)CD45RB(lo)CD62L(-), whereas only a minority of the Foxp3(+)CD4(+)CD25(+) T cells in the spleen and mesenteric lymph nodes showed this phenotype. The Tregs in the small intestinal LP (LP-Tregs) expressed higher levels of CCR4 and CCR9 and a substantially lower level of CCR7 than the Tregs in the spleen. In vitro, the LP-Tregs showed chemotaxis to CCL25/thymus-expressed chemokine. In addition, they showed efficient chemotaxis to the CCR4 ligands, CCL17/thymus and activation-regulated chemokine and CCL22/macrophage-derived chemokine, which are abundantly expressed by dendritic cells (DCs) in the small intestinal LP. In vivo, approximately 50% of the LP-Tregs were closely associated or in direct contact with LP-DCs. These findings demonstrate that LP-Tregs are phenotypically and functionally unique and raise the possibility that they are retained in the small intestinal LP through the action of CCL17 and CCL22, which are locally produced by LP-DCs.
CD4(+)CD25(+)调节性T细胞（Tregs）被认为在抑制肠道中针对自身和非自身抗原的致病性反应中发挥作用。然而，它们在肠道中的精确特性和功能，以及它们募集到肠道的分子基础，目前还知之甚少。在这里，我们发现小肠固有层（LP）中的大多数CD4(+)CD25(+) T细胞表达Foxp3并表现出“效应/记忆”表型，即CD44(hi)CD45RB(lo)CD62L(-)，而脾脏和肠系膜淋巴结中只有少数Foxp3(+)CD4(+)CD25(+) T细胞表现出这种表型。与脾脏中的Tregs相比，小肠LP中的Tregs（LP-Tregs）表达更高水平的CCR4和CCR9，而CCR7水平则显著较低。在体外，LP-Tregs对CCL25/胸腺表达趋化因子表现出趋化性。此外，它们对CCR4配体CCL17/胸腺和活化调节趋化因子以及CCL22/巨噬细胞衍生趋化因子表现出高效趋化性，这些趋化因子在小肠LP中的树突状细胞（DCs）中大量表达。在体内，约50%的LP-Tregs与LP-DCs密切相关或直接接触。这些发现表明，LP-Tregs在表型和功能上具有独特性，并增加了它们通过LP-DCs局部产生的CCL17和CCL22作用而保留在小肠LP中的可能性。
