Nagai Hiroshi, Oniki Shuntaro, Oka Masahiro, Horikawa Tatsuya, Nishigori Chikako
Department of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Arch Dermatol Res. 2006 Aug;298(3):131-4. doi: 10.1007/s00403-006-0668-y. Epub 2006 Jun 20.
Alopecia areata (AA) is generally regarded as an organ-specific autoimmune disease. Although it has been hypothesized that the autoimmunity is mediated by T cells and that hair follicle melanocyte is one of the targets, definitive evidence is lacking. We here demonstrate that AA-like lesions can be induced in mice by inducing CD8(+) T-cell-mediated immunity to hair follicle melanocytes. We found that hair loss was induced in mice-bearing interleukin-12-producing B16 melanoma cells by the depletion of CD4(+) T cells, accompanied by vitiligo-like coat color change. The alopecic lesions varied in size from pachy to extensive. In many instances, hair loss developed and was followed by the regrowth of white hairs. Histological analysis revealed that mononuclear cells infiltrated in and around the bulb region of hair follicles. Furthermore, immunohistochemical examination clearly showed the intra-follicular infiltration of CD8(+) T cells. Neither the vitiligo-like coat color nor AA-like lesions were induced when CD8(+) T cells were codepleted. These observations indicate that the induction of CD8(+) T-cell-mediated immunity against hair follicle melanocytes causes alopecia. It is thought that there are many types of AA with different mechanisms, targets etc. Although hair follicle melanocytes have long been thought to be one of the targets of AA, evidence to support the hypothesis is sparse. Therefore, we believe that our observation is significant to support the hypothesis.
斑秃（AA）通常被认为是一种器官特异性自身免疫性疾病。尽管有假说认为自身免疫是由T细胞介导的，且毛囊黑素细胞是靶标之一，但确凿证据仍很缺乏。我们在此证明，通过诱导针对毛囊黑素细胞的CD8(+) T细胞介导的免疫反应，可在小鼠中诱导出类似斑秃的病变。我们发现，通过清除CD4(+) T细胞，携带产生白细胞介素-12的B16黑色素瘤细胞的小鼠会出现脱发，并伴有类似白癜风的毛色变化。斑秃病变大小不一，从局部增厚到广泛脱发。在许多情况下，先出现脱发，随后长出白色毛发。组织学分析显示，毛囊球部及其周围有单核细胞浸润。此外，免疫组化检查清楚地显示CD8(+) T细胞在毛囊内浸润。当CD8(+) T细胞同时被清除时，既不会诱导出类似白癜风的毛色变化，也不会出现类似斑秃的病变。这些观察结果表明，针对毛囊黑素细胞的CD8(+) T细胞介导的免疫反应诱导会导致脱发。人们认为存在多种机制、靶标等不同的斑秃类型。尽管长期以来一直认为毛囊黑素细胞是斑秃的靶标之一，但支持该假说的证据很少。因此，我们相信我们的观察结果对支持该假说具有重要意义。
