do Canto Fábio Barrozo, Campos Sylvia Maria Nicolau, Granato Alessandra, da Silva Rafael F, de Paiva Luciana Souza, Nóbrega Alberto, Bellio Maria, Fucs Rita
Universidade Federal do Rio de Janeiro (UFRJ), Centro de Ciências da Saúde, Instituto de Microbiologia Paulo de Góes (IMPG), Departamento de Imunologia, Laboratório Integrado de Imunobiologia - Rio de Janeiro/RJ, Brazil.
Universidade Federal Fluminense (UFF), Instituto de Biologia, Departamento de Imunobiologia, Campus do Valonguinho, Outeiro de São João Batista, s/n. Niterói, RJ 24210-130 - Brazil.
Sci Rep. 2016 Jun 29;6:28573. doi: 10.1038/srep28573.
Intestinal inflammation can be induced by the reconstitution of T/B cell-deficient mice with low numbers of CD4(+) T lymphocytes depleted of CD25(+)Foxp3(+) regulatory T cells (Treg). Using RAG-knockout mice as recipients of either splenocytes exclusively depleted of CD25(+) cells or FACS-purified CD4(+)CD25(-)Foxp3(-) T cells, we found that the augmentation of potentially colitogenic naïve T cell numbers in the inoculum was unexpectedly beneficial for the suppression of colon disease and maintenance of immune homeostasis. Protection against T cell-mediated colitis correlated with a significant increment in the frequency of peripherally-induced CD4(+)CD25(+)Foxp3(+) T (pTreg) cells, especially in the mesenteric lymph nodes, an effect that required the presence of B cells and CD4(+)CD25(-)Foxp3(+) cells in physiological proportions. Our findings support a model whereby the interplay between B lymphocytes and a diversified naïve T cell repertoire is critical for the generation of CD4(+)CD25(+)Foxp3(+) pTreg cells and colitis suppression.
通过用低数量的去除了CD25(+)Foxp3(+)调节性T细胞（Treg）的CD4(+)T淋巴细胞重建T/B细胞缺陷小鼠，可诱导肠道炎症。使用RAG基因敲除小鼠作为仅去除了CD25(+)细胞的脾细胞或经荧光激活细胞分选（FACS）纯化的CD4(+)CD25(-)Foxp3(-)T细胞的受体，我们发现接种物中潜在致结肠炎的幼稚T细胞数量的增加意外地有利于抑制结肠疾病和维持免疫稳态。对T细胞介导的结肠炎的保护作用与外周诱导的CD4(+)CD25(+)Foxp3(+)T（pTreg）细胞频率的显著增加相关，尤其是在肠系膜淋巴结中，这一效应需要B细胞和生理比例的CD4(+)CD25(-)Foxp3(+)细胞的存在。我们的研究结果支持这样一种模型，即B淋巴细胞与多样化的幼稚T细胞库之间的相互作用对于CD4(+)CD25(+)Foxp3(+)pTreg细胞的产生和结肠炎抑制至关重要。
