Cavani Andrea, Nasorri Francesca, Ottaviani Chiara, Sebastiani Silvia, De Pità Ornella, Girolomoni Giampiero
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, Rome, Italy.
J Immunol. 2003 Dec 1;171(11):5760-8. doi: 10.4049/jimmunol.171.11.5760.
We investigated the capacity of CD25(+) T regulatory cells (Treg) to modulate T cell responses to nickel, a common cause of allergic contact dermatitis. CD4(+) T cells isolated from the peripheral blood of six healthy, nonallergic individuals showed a limited capacity to proliferate in response to nickel in vitro, but responsiveness was strongly augmented (mean increment +/- SD, 240 +/- 60%) when cells were depleted of CD25(+) Treg. Although CD25(+) Treg were anergic to nickel, a small percentage up-regulated membrane CTLA-4 upon nickel exposure. CD25(+) Treg strongly and dose-dependently inhibited nickel-specific activation of CD25(-) T lymphocytes in coculture experiments in a cytokine-independent, but cell-to-cell contact-dependent, manner. Approximately 30% of circulating CD25(+) Treg expressed the cutaneous lymphocyte-associated Ag (CLA), and CLA(+)CD25(+) Treg were more efficient than CLA(-)CD25(+) cells in suppressing nickel responsiveness of CD25(-) T cells. The site of a negative patch test in response to nickel showed an infiltrate of CD4(+)CLA(+) cells and CD25(+) cells, which accounted for approximately 20% of the total T cells isolated from the tissue. Skin-derived T cells suppressed nickel-specific responses of peripheral blood CD25(-) T cells. In addition, 60 +/- 14% of peripheral blood CD25(+) Treg expressed the chemokine receptor CCR7 and strongly inhibited naive T cell activation in response to nickel. Finally, CD25(+) T cells isolated from peripheral blood of nickel-allergic patients showed a limited or absent capacity to suppress metal-specific CD4(+) and CD8(+) T cell responses. The results indicates that in healthy individuals CD25(+) Treg can control the activation of both naive and effector nickel-specific T cells.
我们研究了CD25(+)调节性T细胞（Treg）调节T细胞对镍（过敏性接触性皮炎的常见病因）反应的能力。从6名健康、无过敏个体的外周血中分离出的CD4(+) T细胞在体外对镍的增殖反应能力有限，但当细胞去除CD25(+) Treg后，反应性显著增强（平均增加±标准差，240±60%）。尽管CD25(+) Treg对镍无反应，但一小部分在接触镍后上调了膜CTLA-4。在共培养实验中，CD25(+) Treg以细胞因子非依赖但细胞间接触依赖的方式强烈且剂量依赖性地抑制CD25(-) T淋巴细胞的镍特异性激活。大约30%的循环CD25(+) Treg表达皮肤淋巴细胞相关抗原（CLA），CLA(+)CD25(+) Treg在抑制CD25(-) T细胞的镍反应性方面比CLA(-)CD25(+)细胞更有效。对镍的阴性斑贴试验部位显示有CD4(+)CLA(+)细胞和CD25(+)细胞浸润，这些细胞约占从组织中分离出的总T细胞的20%。皮肤来源的T细胞抑制外周血CD25(-) T细胞的镍特异性反应。此外，60±14%的外周血CD25(+) Treg表达趋化因子受体CCR7，并强烈抑制幼稚T细胞对镍的激活。最后，从镍过敏患者外周血中分离出的CD25(+) T细胞抑制金属特异性CD4(+)和CD8(+) T细胞反应的能力有限或缺失。结果表明，在健康个体中，CD25(+) Treg可以控制幼稚和效应性镍特异性T细胞的激活。
