CD4+CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype
CD4+CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype
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DOI：
10.1093/intimm/dxm143
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Miyasaka, Masayuki
中科院分区：
文献类型：
--
作者：
Guo, Zijin;Jang, Myoung Ho;Miyasaka, Masayuki
CD 4（+）CD 25（+）调节性T细胞（TCRs）参与抑制肠道中对自身和非自身抗原的致病性应答。然而，它们在肠道中的确切性质和功能，以及它们向肠道募集的分子基础，却知之甚少。我们发现，小肠固有层（LP）中的大多数CD 4（+）CD 25（+）T细胞表达Foxp 3，并表现出“效应/记忆”表型，CD 44（hi）CD 45 RB（lo）CD 62 L（-），而脾脏和肠系膜淋巴结中只有少数Foxp 3（+）CD 4（+）CD 25（+）T细胞表现出这种表型。小肠LP中的TCR 4（LP-TCR 4）表达水平高于脾脏中的TCR 4和CCR 9，而CCR 7表达水平显著低于脾脏中的TCR 7。在体外，LP-T细胞对CCL 25/胸腺表达的趋化因子表现出趋化性。此外，它们对CCR 4配体、CCL 17/胸腺和活化调节趋化因子以及CCL 22/巨噬细胞衍生的趋化因子表现出有效的趋化性，这些趋化因子在小肠LP中由树突状细胞（DC）大量表达。在体内，接近50%的LP-TdR与LP-DCs密切相关或直接接触。这些发现表明，LP-T细胞在表型和功能上是独特的，并且提高了它们通过由LP-DC局部产生的CCL 17和CCL 22的作用保留在小肠LP中的可能性。
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, similar to 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.