Schmutz Sandrine, Bosco Nabil, Chappaz Stephane, Boyman Onur, Acha-Orbea Hans, Ceredig Rhodri, Rolink Antonius G, Finke Daniela
Division of Developmental Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
J Immunol. 2009 Aug 15;183(4):2217-21. doi: 10.4049/jimmunol.0802911. Epub 2009 Jul 27.
During fetal life, CD4(+)CD3(-) lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer's patch development in mice. In adult animals, CD4(+)CD3(-) cells are found in low numbers in lymphoid organs. Whether adult CD4(+)CD3(-) cells are LTi cells and are generated and maintained through cytokine signals has not been directly addressed. In this study we show that adult CD4(+)CD3(-) cells adoptively transferred into neonatal CXCR5(-/-) mice induced the formation of intestinal lymphoid tissues, demonstrating for the first time their bona fide LTi function. Increasing IL-7 availability in wild-type mice either by IL-7 transgene expression or treatment with IL-7/anti-IL-7 complexes increased adult LTi cell numbers through de novo generation from bone marrow cells and increased the survival and proliferation of LTi cells. Our observations demonstrate that adult CD4(+)lineage(-) cells are LTi cells and that the availability of IL-7 determines the size of the adult LTi cell pool.
在胎儿期,CD4(+)CD3(-)淋巴组织诱导细胞(LTi细胞)对于小鼠淋巴结和派尔集合淋巴结的发育是必需的。在成年动物中,在淋巴器官中可发现少量的CD4(+)CD3(-)细胞。成年CD4(+)CD3(-)细胞是否为LTi细胞以及是否通过细胞因子信号产生和维持尚未得到直接解决。在本研究中,我们表明,过继转移到新生CXCR5(-/-)小鼠体内的成年CD4(+)CD3(-)细胞诱导了肠道淋巴组织的形成,首次证明了它们真正的LTi功能。通过IL-7转基因表达或用IL-7/抗IL-7复合物处理来增加野生型小鼠体内IL-7的可利用性,可通过从骨髓细胞重新生成来增加成年LTi细胞数量,并增加LTi细胞的存活和增殖。我们的观察结果表明,成年CD4(+)谱系(-)细胞是LTi细胞,并且IL-7的可利用性决定了成年LTi细胞库的大小。