Holán V, Kuffová L, Zajícová A, Krulová M, Filipec M, Holler P, Jancárek A
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague.
J Immunol. 1998 Oct 1;161(7):3237-41.
The immunosuppressive effects of UV radiation have been well documented. This suppression has been attributed to the action of the cis form of urocanic acid (UCA), a photoproduct of trans-UCA, a natural constituent of the skin. Here, we show that mouse spleen cells preincubated with cis-UCA have a diminished proliferative response to allogeneic cells in MLC and to stimulation with anti-CD3 mAb. Cells preincubated with cis-UCA also had a decreased ability to serve as APC and to stimulate the proliferation of allogeneic lymphocytes in MLC. Simultaneously, the production of IL-2 and IFN-gamma by cells preincubated with cis-UCA was decreased. However, IL-10 gene expression and IL-10 protein secretion by spleen cells stimulated in the presence of cis-UCA were significantly enhanced. The principal cell population displaying the cis-UCA-induced elevated production of IL-10 was CD4+ T cells, which were shown to be a direct target of cis-UCA action. This was also supported by the observation that production of IL-10 by stimulated splenic non-T cells or by macrophages was not altered by cis-UCA. The enhanced production of IL-10 by activated CD4+ T cells may represent a novel pathway of UVB radiation-induced, cis-UCA-mediated immunosuppression. We suggest that the elevated production of IL-10 by activated CD4+ T cells may account for the suppressor T cell phenomena described in UV-irradiated recipients.
紫外线辐射的免疫抑制作用已有充分记载。这种抑制作用归因于尿刊酸（UCA）顺式异构体的作用，UCA顺式异构体是反式UCA的光产物，而反式UCA是皮肤的一种天然成分。在此，我们表明，预先用顺式UCA孵育的小鼠脾细胞在混合淋巴细胞培养（MLC）中对同种异体细胞以及抗CD3单克隆抗体刺激的增殖反应减弱。预先用顺式UCA孵育的细胞作为抗原呈递细胞（APC）以及在MLC中刺激同种异体淋巴细胞增殖的能力也降低。同时，预先用顺式UCA孵育的细胞产生白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）的量减少。然而，在顺式UCA存在下刺激的脾细胞中，IL-10基因表达和IL-10蛋白分泌显著增强。显示顺式UCA诱导的IL-10产生增加的主要细胞群体是CD4 + T细胞，已证明其是顺式UCA作用的直接靶点。这也得到以下观察结果的支持，即受刺激的脾非T细胞或巨噬细胞产生的IL-10不受顺式UCA的影响。活化的CD4 + T细胞增强的IL-10产生可能代表紫外线B辐射诱导的、顺式UCA介导的免疫抑制的新途径。我们认为，活化的CD4 + T细胞IL-10产生增加可能解释了紫外线照射受体中描述的抑制性T细胞现象。
