Activation of nickel-specific CD4+ T lymphocytes in the absence of professional antigen-presenting cells
Activation of nickel-specific CD4+ T lymphocytes in the absence of professional antigen-presenting cells
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DOI：
10.1046/j.0022-202x.2001.01574.x
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发表时间：
2002-01-01
影响因子：
6.5
通讯作者：
Cavani, A
中科院分区：
文献类型：
--
作者：
Nasorri, F;Sebastiani, S;Cavani, A
过敏性接触性皮炎由对半抗原的过度T细胞反应引起。树突状细胞是引发半抗原致敏所必需的，但它们可能不是疾病表达所必需的。在这里，我们研究了从6个过敏个体的血液中分离的镍特异性CD 4（+）淋巴细胞的抗原呈递细胞的需求。一个显着的比例（42 121; 35%）的T细胞克隆体外增殖镍也在专业的抗原呈递细胞的情况下，表明直接的T-T半抗原呈递。抗原呈递细胞非依赖性T细胞表现出主要的辅助性T细胞1表型。镍识别这些T细胞主要组织相容性复合物II类限制，不受CD 28触发，独立于他们的激活状态，并不需要处理。该T细胞亚群被镍直接刺激的能力不是由于独特的抗原呈递特性，因为抗原呈递细胞依赖性和抗原呈递细胞非依赖性克隆都显示出相当水平的HLA-DR、CD 80和CD 86，并且同样能够将镍呈递给抗原呈递细胞非依赖性克隆。相反，两种T细胞类型都不能激活抗原呈递细胞依赖性T淋巴细胞。T-T呈递诱导T细胞受体下调、CD 25、CD 80、CD 86和HLA-DR上调以及干扰素-γ释放，尽管与树突状细胞-T呈递诱导的那些相比程度较低。在T-T呈递后，克隆没有经历无反应性，并且保持了对抗原脉冲的树突状细胞的反应能力。总之，我们的数据表明，抗原呈递细胞独立的T细胞活化可以有效地放大半抗原特异性免疫应答。
Allergic contact dermatitis ensues from exaggerated T cell responses to haptens. Dendritic cells are required for the initiation of hapten sensitization, but they may not be necessary for disease expression. Here we investigated the antigen-presenting cell requirement of nickel-specific CD4(+) lymphocytes isolated from the blood of six allergic individuals. A significant proportion (42 out of 121; 35%) of the T cell clones proliferated hi vitro to nickel also in the absence of professional antigen-presenting cells, suggesting a direct T-T hapten presentation. Antigen-presenting-cell-independent T cells showed a predominant T helper 1 phenotype. Nickel recognition by these T cells was major histocompatibility complex class II restricted, not influenced by CD28 triggering, independent from their state of activation, and did not require processing. The capacity of this T cell subset to be directly stimulated by nickel was not due to unique antigen-presenting properties, as both antigen-presenting-cell-dependent and antigen-presenting-cell-independent clones displayed comparable levels of HLA-DR, CD80, and CD86, and were equally capable of presenting nickel to antigen-presenting-cell-independent clones. In contrast, neither T cell types activated antigen-presenting-cell-dependent T lymphocytes. T-T presentation induced T cell receptor downregulation, CD25, CD80, CD86, and HLA-DR upregulation, and interferon-gamma release, although to a lesser extent compared to those induced by dendritic cell-T presentation. Following T-T presentation, the clones did not undergo unresponsiveness and maintained the capacity to respond to dendritic cells pulsed with antigen. In aggregate, our data suggest that antigen-presenting-cell-independent T cell activation can effectively amplify hapten-specific immune responses.