Yagi H, Tokura Y, Wakita H, Furukawa F, Takigawa M
Department of Dermatology, Hamamatsu University School of Medicine, Japan.
J Immunol. 1996 Mar 1;156(5):1824-31.
In murine contact photosensitivity, a cutaneous delayed-type hypersensitivity reaction, preirradiation of the photosensitization site with UVB induced Ag-specific, afferent limb-acting, CD4+CD8- suppressor T cells (Ts). The present study examined usage of TCR V beta and production of immunosuppressive cytokines in Ts propagated in vitro. Spleen cells from UVB-preirradiated, 3,3',4',5- tetracholorosalicylanilide (TCSA)-photosensitized mice were stimulated with 3000-rad-irradiated lymph node cells (LNC) from TCSA/UVA-sensitized mice (LNCTCSA) in the presence of rIL-t. After several rounds of antigenic stimulation, a T cell line (B+TCL) consisted exclusively of CD3+CD4+CD8- V beta 7+ and V beta 13+ populations. Transfer to naive recipients of B+TCL treated with anti-V beta mAb plus complement revealed that the V beta 7+ cells suppressed both the in vivo and the in vitro aspects of contact photosensitivity to TCSA in an Ag-specific manner. The in vitro suppressive activity of B+TCL was neutralized by anti-IL-10 mAb, but not by anti-IL-4 mAb, indicating a crucial role of IL-10 in UBV-induced suppression. Upon stimulation with 3000-rad-irradiated-LNCTCSA, B+TCL released IL-4 and IL-10 but not IL-2, and V beta 7+ cells produced IL-10. The reverse transcriptase-PCR detected mRNA for IL-4 and IL-10 but not that for IL-2, IFN-gamma, or TGF-beta in B+TCL stimulated with or without concanavalin A. In accordance with the findings in B+TCL, spleen cells from UVB preirradiation plus TCSA/UVA mice contained V beta 7+ T cells that suppressed contact photosensitivity to TCSA and produced substantial amounts of IL-4 that provided a microenvironment for Th2 cell generation. We conclude that UVB preirradiation and photosensitization result in the generation of V beta 7+ Th2 cells that suppress contact photosensitivity by releasing IL-10. The dysfunction of effector Th1 cells underlying UVB suppression of delayed-type hypersensitivity seems to be due not only to altered APC function but also to counteraction of Th2 cells by Th1 cells.
在小鼠接触性光敏感反应（一种皮肤迟发型超敏反应）中，用中波紫外线（UVB）预先照射光敏化部位可诱导产生抗原特异性、作用于传入支的CD4 + CD8 - 抑制性T细胞（Ts）。本研究检测了体外增殖的Ts细胞中T细胞受体Vβ的使用情况以及免疫抑制性细胞因子的产生。将来自经UVB预先照射、用3,3',4',5 - 四氯水杨酰苯胺（TCSA）进行光敏化处理的小鼠的脾细胞，在重组白细胞介素 - t（rIL - t）存在的情况下，用来自经TCSA/长波紫外线（UVA）致敏的小鼠的3000拉德照射的淋巴结细胞（LNC）（LNCTCSA）进行刺激。经过几轮抗原刺激后，获得了一个T细胞系（B + TCL），该细胞系仅由CD3 + CD4 + CD8 - Vβ7 + 和Vβ13 + 细胞群体组成。将用抗Vβ单克隆抗体加补体处理过的B + TCL转移至未致敏的受体，结果显示Vβ7 + 细胞以抗原特异性方式抑制了对TCSA的接触性光敏感反应的体内和体外表现。B + TCL的体外抑制活性可被抗白细胞介素 - 10（IL - 10）单克隆抗体中和，但不能被抗IL - 4单克隆抗体中和，这表明IL - 10在UVB诱导的抑制中起关键作用。在用3000拉德照射的LNCTCSA刺激后，B + TCL释放IL - 4和IL - 10，但不释放IL - 2，且Vβ7 + 细胞产生IL - 10。逆转录聚合酶链反应（RT - PCR）检测到在用或不用伴刀豆球蛋白A刺激的B + TCL中，有IL - 4和IL - 10的信使核糖核酸（mRNA），但没有IL - 2、干扰素 - γ（IFN - γ）或转化生长因子 - β（TGF - β）的mRNA。与B + TCL中的发现一致，来自UVB预先照射加TCSA/UVA小鼠的脾细胞含有Vβ7 + T细胞，这些细胞抑制对TCSA的接触性光敏感反应，并产生大量的IL - 4，为辅助性T细胞2（Th2）的生成提供了微环境。我们得出结论，UVB预先照射和光敏化导致Vβ7 + Th2细胞的产生，这些细胞通过释放IL - 10来抑制接触性光敏感反应。UVB对迟发型超敏反应的抑制作用背后的效应性Th1细胞功能障碍似乎不仅是由于抗原呈递细胞（APC）功能改变，还由于Th2细胞对Th1细胞的对抗作用。
