IL-17-and IFN-γ-Secreting Foxp3+ T Cells Infiltrate the Target Tissue in Experimental Autoimmunity
IL-17-and IFN-γ-Secreting Foxp3+ T Cells Infiltrate the Target Tissue in Experimental Autoimmunity
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DOI：
10.4049/jimmunol.1001519
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发表时间：
2010-12-15
影响因子：
4.4
通讯作者：
Furlan, Roberto
中科院分区：
文献类型：
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作者：
Esposito, Marianna;Ruffini, Francesca;Furlan, Roberto
CD 4（+）Foxp 3（+）调节性T细胞（TCRs）被认为在控制免疫系统稳态中至关重要，并且它们的紊乱通常与自身免疫相关。然而，识别T细胞是困难的，因为大多数标记物，包括CD 25和Foxp 3，是由最近激活的T细胞共享的。我们在这篇论文中表明，CD 4（+）Foxp 3（+）T细胞在免疫时在外周淋巴器官中产生，并容易在自身免疫反应的靶器官中积累，与经典的炎症细胞一起，构成高达50%的浸润性CD 4（+）T细胞。然而，大多数CD 4（+）Foxp 3（+）T细胞是CD 25（-），并表达促炎细胞因子，如IL-17和IFN-γ，质疑其抑制性质。此外，在体外的幼稚和自身免疫性小鼠的CD 4（+）T淋巴细胞，刺激分化为Th 1，Th 2，Th 17，并诱导T淋巴细胞，显示谱系特异性标志物的早期混合表达。这些结果清楚地指出了幼稚CD 4（+）T细胞前所未有的可塑性，整合炎症信号可能会改变它们的命运，从最初的谱系定型到不同的功能表型。免疫学杂志，2010，185：7467-7473。
CD4(+)Foxp3(+) regulatory T cells (Tregs) have been considered crucial in controlling immune system homeostasis, and their derangement is often associated to autoimmunity. Tregs identification is, however, difficult because most markers, including CD25 and Foxp3, are shared by recently activated T cells. We show in this paper that CD4(+)Foxp3(+) T cells are generated in peripheral lymphoid organs on immunization and readily accumulate in the target organ of an autoimmune reaction, together with classical inflammatory cells, constituting up to 50% of infiltrating CD4(+)T cells. Most CD4(+)Foxp3(+) T cells are, however, CD25(-) and express proinflammatory cytokines such as IL-17 and IFN-gamma, questioning their suppressive nature. Moreover, in vitro CD4(+) T lymphocytes from naive and autoimmune mice, stimulated to differentiate into Th1, Th2, Th17, and induced Tregs, display early mixed expression of lineage-specific markers. These results clearly point to an unprecedented plasticity of naive CD4(+) T cells, that integrating inflammatory signals may change their fate from the initial lineage commitment to a different functional phenotype. The Journal of Immunology, 2010, 185: 7467-7473.