MHC class II-KO mice are resistant to the immunosuppressive effects of UV light.
MHC class II-KO mice are resistant to the immunosuppressive effects of UV light.
复制标题
MHC II 类-KO 小鼠对紫外线的免疫抑制作用具有抵抗力。
DOI：
10.1097/00007890-198801000-00042
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
J. Nicolas
中科院分区：
文献类型：
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作者：
M. Krasteva;F. Aubin;Sandrine Laventurier;J. Kehren;O. Assossou;Jean Kanitakis;D. Kaiserlian;J. Nicolas
紫外线B通过抑制皮肤细胞免疫反应导致皮肤癌的发生。在这里，我们解决了uvb诱导免疫抑制的机制问题。我们使用了抗原特异性皮肤炎症模型，即对DNFB的接触超敏反应（CHS）反应，该反应由CD8+效应T细胞介导，并由CD4+ T细胞下调。我们发现UVB对CD4+和CD8+ T细胞有相反的作用。UVB照射减少了淋巴器官中活化的CD8+ T细胞的数量，并损害了它们的功能活性。这导致在攻击部位产生ifn - γ的CD8+ T细胞浸润不足，从而无法发生抗原特异性CHS反应。这种作用是由CD4+抑制细胞介导的，因为在缺乏CD4+ T细胞的情况下（MHC类II-KO小鼠和CD4+ T细胞缺失小鼠），UVB没有免疫抑制作用。事实上，uvb照射的CD4+ T细胞缺陷小鼠在淋巴器官中产生ifn - γ的半抗原特异性CD8+ T细胞的频率正常，并且对DNFB产生正常的CHS反应。因此，在没有CD4+ T细胞的情况下，UVB不会改变MHC i类限制性CD8+效应T细胞的启动。总的来说，这些数据表明，uvb诱导的免疫抑制是继发于CD4+抑制性T细胞的优先激活，而不是CD8+效应T细胞群的缺陷启动和扩增。这可能对预防紫外线诱发的皮肤癌具有重要意义。
Ultraviolet B light is responsible for the development of skin cancer through inhibition of cellular immune responses in the skin. Here, we addressed the question of the mechanisms involved in UVB-induced immune suppression. We used a model of antigen-specific skin inflammation, the contact hypersensitivity (CHS) reaction to DNFB, which is mediated by CD8+ effector T cells and down-regulated by CD4+ T cells. We show that UVB have opposite effects on CD4+ and CD8+ T cells. UVB irradiation reduced the number of activated CD8+ T cells in the lymphoid organs and impaired their functional activity. This resulted in deficient infiltration of IFN-gamma producing CD8+ T cells at challenged site and consequently in the inability to develop an antigen-specific CHS reaction. This effect is mediated by CD4+ suppressor cells, since in the absence of CD4+ T cells (MHC class II-KO mice and CD4+ T cell-depleted mice), UVB have no immunosuppressive effects. Indeed, UVB-irradiated CD4+ T cell-deficient mice have a normal frequency of IFN-gamma-producing hapten-specific CD8+ T cells in the lymphoid organs and develop a normal CHS reaction to DNFB. Thus, in the absence of CD4+ T cells, UVB do not alter the priming of MHC class I-restricted CD8+ effector T cells. Collectively, these data show that UVB-induced immune suppression is secondary to preferential activation of CD4+ suppressor T cells and not to deficient priming and expansion of the effector CD8+ T cell population. This may have important implications for the prevention of UV-induced skin cancers.