Moulon C, Wild D, Dormoy A, Weltzien H U
Max-Planck-Institut for Immunbiology, Freiburg, Germany.
J Invest Dermatol. 1998 Sep;111(3):360-6. doi: 10.1046/j.1523-1747.1998.00306.x.
T lymphocytes are critical effectors in the pathogenesis of contact hypersensitivity. Nickel is the most common contact sensitizer in humans and nickel-specific CD4+ T helper cells have been extensively characterized. Because recent observations have suggested the activation of CD8+ T cells in murine models of contact hypersensitivity, we investigated the existence of CD8+ hapten-specific T lymphocytes in patients with allergy to nickel. Nickel-specific T cell lines were generated from the peripheral blood of three allergic donors. The T cell lines were composed of a majority of CD4+ T cells, but CD8+ T cells were also present and their percentage increased with repeated in vitro stimulations. In addition to nickel-reactive helper T cell-0-type or helper T cell-2-type CD4+ T cell clones, CD8+ T cell clones could be derived from these cell lines and a total of 15 clones were further studied. Cytokine production was evaluated for 11 CD8+ T cell clones that were either cytotoxic T cell-0- or cytotoxic T cell-1-type clones. Additional effector functions were investigated on the complete panel of T cell clones. These CD8+ T cells did not only display hapten-specific proliferation, but also specific cytotoxic activities towards autologous EBV-B cells in the presence of nickel. Two different types of CD8+ T cells were characterized. Most of the clones lysed only autologous targets in the constant presence of nickel; however, one clone was able to lyse numerous targets in the presence of NiSO4, irrespective of the expression of either major histocompatibility complex class I or class II molecules. The characterization of nickel-specific cytotoxic CD8+ T cells with different requirements for nickel-specific target lysis, may have important implications in the development or in the control of human contact hypersensitivity reactions to nickel in vivo.
T淋巴细胞是接触性超敏反应发病机制中的关键效应细胞。镍是人类最常见的接触性致敏原，镍特异性CD4+辅助性T细胞已得到广泛研究。由于最近的观察结果表明在接触性超敏反应的小鼠模型中CD8+ T细胞被激活，我们研究了对镍过敏患者中CD8+半抗原特异性T淋巴细胞的存在情况。从三名过敏供体的外周血中产生了镍特异性T细胞系。这些T细胞系主要由CD4+ T细胞组成，但也存在CD8+ T细胞，并且随着体外反复刺激其百分比增加。除了镍反应性辅助性T细胞0型或辅助性T细胞2型CD4+ T细胞克隆外，还可以从这些细胞系中获得CD8+ T细胞克隆，共对15个克隆进行了进一步研究。对11个细胞毒性T细胞0型或细胞毒性T细胞1型的CD8+ T细胞克隆评估了细胞因子产生情况。在完整的T细胞克隆组中研究了其他效应功能。这些CD8+ T细胞不仅表现出半抗原特异性增殖，而且在有镍存在的情况下对自体EBV - B细胞具有特异性细胞毒性活性。鉴定出了两种不同类型的CD8+ T细胞。大多数克隆仅在持续存在镍的情况下裂解自体靶细胞；然而，一个克隆在有NiSO4存在时能够裂解许多靶细胞，而与主要组织相容性复合体I类或II类分子的表达无关。对镍特异性靶细胞裂解有不同要求的镍特异性细胞毒性CD8+ T细胞的鉴定，可能对体内人类对镍的接触性超敏反应的发生或控制具有重要意义。
