Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice
Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice
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DOI：
10.1046/j.1523-1747.2000.00113.x
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发表时间：
2000-10-01
影响因子：
6.5
通讯作者：
Hoffmann, R
中科院分区：
文献类型：
--
作者：
Freyschmidt-Paul, P;Seiter, S;Hoffmann, R
据报道，一种小鼠cd44v10中和抗体可损害延迟型超敏反应。由于斑秃的特点是延迟型超敏反应样T细胞介导的免疫反应，我们解决了抗cd44v10抗体是否影响斑秃发病的问题。因此，我们采用C3H/HeJ小鼠模型，通过移植小鼠斑秃皮损，诱导未患小鼠斑秃。6只移植小鼠腹腔注射抗cd44v10, 6只移植小鼠腹腔注射抗cd44v10, 6只移植小鼠腹腔注射抗cd44v10, 6只移植小鼠腹腔注射磷酸缓冲盐水。11周后，注射磷酸盐缓冲盐水的动物平均出现了36.8%的斑秃。在抗cd44标准治疗的小鼠中，脱发的发生时间略有延迟，其程度减少到身体的17.2%。相比之下，6只抗cd44v10治疗的小鼠中有5只没有出现任何脱发现象，一只小鼠只有1%的身体出现斑秃。免疫组织化学检查显示，与磷酸盐缓冲盐水或抗cd44标准处理的小鼠相比，抗cd44v10处理的小鼠毛囊上皮上CD8（+）淋巴细胞和CD4（+）细胞的显著减少，以及主要组织相容性复合体I类的表达减少。我们的数据显示，抗cd44v10能够抑制C3H/HeJ小鼠斑秃的发生。这可能是通过抗cd44v10触发的免疫细胞归巢损伤（例如CD8(+) T细胞），导致其在靶组织中的数量减少来实现的。
A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8(+) lymphocytes and, to a lesser degree, CD4(+) cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8(+) T cells), resulting in a decrease of their number in target tissues.