CD4+ T cells regulate CD8+ T cell-mediated cutaneous immune responses by restricting effector T cell development through a Fas ligand-dependent mechanism
CD4+ T cells regulate CD8+ T cell-mediated cutaneous immune responses by restricting effector T cell development through a Fas ligand-dependent mechanism
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DOI：
10.4049/jimmunol.172.4.2286
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发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Fairchild, RL
中科院分区：
文献类型：
--
作者：
Gorbachev, AV;Fairchild, RL
CD8(+) T 细胞介导的皮肤对半抗原致敏和激发、接触超敏反应 (CHS) 反应的强度和持续时间，受到 CD4(+) T 细胞通过未知机制的负调节。在这项研究中，我们发现CD4(+) T 细胞限制了介导CHS 对2,4-二硝基氟苯反应的半抗原特异性CD8(+) T 细胞的发育和扩增。在缺乏CD4+T细胞的情况下，致敏后第5天，在皮肤引流淋巴结中检测到大量产生IFN-γ的半抗原特异性CD8+T细胞，这些数量略有下降，但一直维持到第9天，这与在这些小鼠中观察到的CHS反应的强度和持续时间的增加相关。在CD4（+）T细胞存在的情况下，致敏后第5天检测到的产生IFN-γ的半抗原特异性CD8（+）T细胞数量较低，并在第7天迅速降至背景水平。效应CD8（+）T细胞发育有限与淋巴启动位点中半抗原呈递树突状细胞数量减少有关。 Fas配体缺陷的gld小鼠致敏后，这种形式的免疫调节不存在。将野生型CD4(+) T细胞转移至gld小鼠体内可恢复gld小鼠中CD8(+) T细胞启动的负调节和对半抗原攻击的免疫反应。这些结果表明CD4(+) T 细胞通过Fas 配体依赖性机制限制半抗原特异性CD8(+) T 细胞引发CHS 反应。
The magnitude and duration of CD8(+) T cell-mediated responses in the skin to hapten sensitization and challenge, contact hypersensitivity (CHS), is negatively regulated by CD4(+) T cells through an unknown mechanism. In this study we show that CD4(+) T cells restrict the development and expansion of hapten-specific CD8(+) T cells mediating CHS responses to 2,4-dinitrofluorobenzene. In the absence of CD4(+) T cells, high numbers of hapten-specific CD8(+) T cells producing IFN-gamma were detected in the skin-draining lymph nodes on day 5 postsensitization, and these numbers decreased slightly, but were maintained through day 9, correlating with the increased magnitude and duration of CHS responses observed in these mice. In the presence of CD4(+) T cells, the number of hapten-specific CD8(+) T cells producing IFN-gamma detected on day 5 postsensitization was lower and quickly fell to background levels by day 7. The limited development of effector CD8(+) T cells was associated with decreased numbers of hapten-presenting dendritic cells in the lymphoid priming site. This form of immunoregulation was absent after sensitization of Fas ligand-defective gld mice. Transfer of wild-type CD4(+) T cells to gld mice restored the negative regulation of CD8(+) T cell priming and the immune response to hapten challenge in gld-recipient mice. These results indicate that CD4(+) T cells restrict hapten-specific CD8(+) T cell priming for CHS responses through a Fas ligand-dependent mechanism.