Palermo Belinda, Garbelli Silvia, Mantovani Stefania, Scoccia Elisabetta, Da Prada Gian Antonio, Bernabei Paola, Avanzini M Antonietta, Brazzelli Valeria, Borroni Giovanni, Giachino Claudia
Experimental Immunology Laboratory, IRCCS Maugeri Foundation, Pavia, Italy.
Eur J Immunol. 2005 Nov;35(11):3153-62. doi: 10.1002/eji.200535110.
Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor down-regulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-gamma production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocyte-specific cytotoxic responses differs between the two pathologies.
白癜风是一种皮肤疾病，其特征为继发于黑素细胞丧失的色素脱失斑。一个不寻常的方面是它与黑色素瘤的关系：在这两种病症中均发现了针对黑素细胞抗原的细胞毒性T淋巴细胞，这意味着耐受性的破坏，然而所产生的免疫反应却是相反的。导致这些相反效应的机制尚不清楚。在此，我们对这两种疾病中整个黑素细胞特异性T细胞群体进行了直接比较。我们证明，Melan-A/MART-1特异性T淋巴细胞的前体频率及其激活状态均无显著差异。然而，通过使用基于四聚体的T细胞受体下调试验，我们记录到白癜风T细胞具有更高的亲和力。我们计算得出，两种疾病之间使50%的受体达到最大下调所需的肽浓度相差6.5倍。此外，仅白癜风T细胞能够针对HLA匹配的黑色素瘤细胞进行有效的受体下调和产生γ干扰素，这表明这种受体亲和力的差异具有生理相关性。通过分析从这两种疾病中分离出的Melan-A/MART-1特异性克隆，证实了受体亲和力和肿瘤反应性的差异。我们的结果表明，这两种病理状态下黑素细胞特异性细胞毒性反应的质量而非数量有所不同。
