IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells
IFN-α and IL-10 induce the differentiation of human type 1 T regulatory cells
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DOI：
10.4049/jimmunol.166.9.5530
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Roncarolo, MG
中科院分区：
文献类型：
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作者：
Levings, MK;Sangregorio, R;Roncarolo, MG
1型调节性CD4⁺T（Tr1）细胞在体外和体内均可抑制抗原特异性免疫反应。尽管白细胞介素 - 10（IL - 10）对Tr1细胞的分化至关重要，但其他细胞因子在初始T细胞分化为Tr1细胞过程中的作用尚未得到研究。在此我们证明，内源性或外源性IL - 10与干扰素 -α（IFN -α）联合，但不与转化生长因子 -β（TGF -β）联合，可诱导源自脐带血的初始CD4⁺T细胞分化为Tr1细胞：IL - 10⁺、干扰素 -γ⁺、白细胞介素 - 2（- /低）、白细胞介素 - 4（-）。源自外周血的初始CD4⁺T细胞需要外源性IL - 10和IFN -α才能分化为Tr1细胞。经抗CD3和抗CD28单克隆抗体激活后，含Tr1细胞的淋巴细胞群的增殖反应降低。同样，含Tr1细胞的培养物通过一种部分由IL - 10和TGF -β介导的机制，对同种异体抗原的反应降低。更重要的是，含Tr1细胞的群体强烈抑制初始T细胞对同种异体抗原的反应。总之，这些结果表明，IFN -α强烈增强IL - 10诱导的功能性Tr1细胞的分化，这是确定特定培养条件以产生用于生物和生化分析以及用于细胞治疗以诱导人类外周耐受的调节性T细胞的重要的第一步。
CD4(+) T regulatory type 1 (Tr1) cells suppress Ag-specific immune responses in vitro and in vivo. Although IL-10 is critical for the differentiation of Tr1 cells, the effects of other cytokines on differentiation of naive T cells into Tr1 cells have not been investigated. Here we demonstrate that endogenous or exogenous IL-10 in combination with IFN-alpha, but not TGF-beta, induces naive CD4(+) T cells derived from cord blood to differentiate into Tt1 cells: IL-10(+)IFN-gamma +IL-2(-/low)IL-4(-). Naive CD4(+) T cells derived from peripheral blood require both exogenous IL-10 and IFN-alpha for Tr1 cell differentiation. The proliferative responses of the Tr1-containing lymphocyte populations, following activation with anti-CD3 and anti-CD28 mAbs, were reduced. Similarly, cultures containing Tr1 cells displayed reduced responses to alloantigens via a mechanism that was partially mediated by IL-10 and TGF-beta. More importantly, Tr1-containing populations strongly suppressed responses of naive T cells to alloantigens. Collectively, these results show that IFN-alpha strongly enhances IL-10-induced differentiation of functional Tri cells, which represents a first major step in establishing specific culture conditions to generate T regulatory cells for biological and biochemical analysis, and for cellular therapy to induce peripheral tolerance in humans.