Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.
Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells.
复制标题
DOI：
10.1084/jem.184.1.19
复制
发表时间：
1996-07-01
期刊：
影响因子：
--
通讯作者：
Roncarolo MG
中科院分区：
文献类型：
--
作者：
Groux H;Bigler M;de Vries JE;Roncarolo MG
在外源性白介素10的存在下，由同种异体单核细胞在初级混合淋巴细胞反应中激活的人CD4+T细胞，在用相同的同种异体抗原重新刺激后，特别是不能增殖。在外源性IL-10存在的情况下，由交联型抗CD3单抗(MAbs)激活的CD4+T细胞可以诱导类似的T细胞无反应状态。无能T细胞不能产生IL-2、IL-5、IL-10、干扰素-γ、肿瘤坏死因子α和粒细胞/巨噬细胞集落刺激因子。IL-10诱导的失能状态持续时间较长。CD3和CD28表达正常，但经抗CD3和抗CD28单抗刺激后，T细胞无能不能逆转。此外，抗CD3单抗再刺激失能T细胞可诱导正常的钙离子流，并导致CD3、CD28和II类主要组织相容性复合体表达增加，表明钙调神经磷酸酶介导的信号转导在这些无能细胞中发生。然而，IL-2受体α链的表达没有上调，这可能是外源性IL-2未能逆转无能状态的原因。有趣的是，无能T细胞和它们的非无能T细胞在佛波酯和钙离子载体激活后显示出相似的增殖和细胞因子产生水平，这表明直接激活蛋白激酶C依赖的途径可以克服IL-10的耐受作用。综上所述，这些数据表明，IL-10诱导T细胞无能，因此可能在诱导和维持抗原特异性T细胞耐受中发挥重要作用。
Human CD4+ T cells, activated by allogeneic monocytes in a primary mixed lymphocyte reaction in the presence of exogenous interleukin (IL) 10, specifically failed to proliferate after restimulation with the same alloantigens. A comparable state of T cell unresponsiveness could be induced by activation of CD4+ T cells by cross-linked anti-CD3 monoclonal antibodies (mAbs) in the presence of exogenous IL-10. The anergic T cells failed to produce IL-2, IL-5, IL-10, interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony- stimulating factor. The IL-10-induced anergic state was long-lasting. T cell anergy could not be reversed after restimulation of the cells with anti-CD3 and anti-CD28 mAbs, although CD3 and CD28 expression was normal. In addition, restimulation of anergized T cells with anti-CD3 mAbs induced normal Ca2+ fluxes and resulted in increased CD3, CD28, and class II major histocompatibility complex expression, indicating that calcineurin-mediated signaling occurs in these anergic cells. However, the expression of the IL-2 receptor alpha chain was not upregulated, which may account for the failure of exogenous IL-2 to reverse the anergic state. Interestingly, anergic T cells and their nonanergic counterparts showed comparable levels of proliferation and cytokine production after activation with phorbol myristate acetate and Ca2+ ionophore, indicating that a direct activation of a protein kinase C-dependent pathway can overcome the tolerizing effect of IL-10. Taken together, these data demonstrate that IL-10 induces T cell anergy and therefore may play an important role in the induction and maintenance of antigen-specific T cell tolerance.