A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis.
A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis.
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DOI：
10.4049/jimmunol.1100657
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Geiger TL
中科院分区：
文献类型：
--
作者：
Alli R;Nguyen P;Boyd K;Sundberg JP;Geiger TL
斑秃是最常见的自身免疫性疾病之一，但与其他自身免疫性疾病相比尚未得到很好的研究。这在一定程度上是由于C3H/HeJ小鼠和Debr大鼠模型系统的局限性，这些模型系统最常用于研究这种疾病，表现出频率低和发病晚。我们描述了一种新的自发性斑秃高发模型。1MOG244T细胞表达双TCRA链，其中一条与单链TCRB结合，可促进毛囊特异性CD8+T细胞的发育。表达该TCR的逆转录病毒转基因小鼠发生自发性斑秃的发生率几乎为100%。疾病最初遵循网状模式，伴随着区域性周期性的脱发和再生，最终进展为全面性脱发。脱发的发生与CD8+T细胞激活、迁移到毛囊内区域和毛囊破坏有关。这种疾病可能与T淋巴细胞过继转移，并且是I类而不是II类MHC依赖。病理性T细胞在疾病早期主要表达IFNG和IL17，随着疾病的进展，细胞因子的产生和IL4和IL10的募集急剧增加。抑制单个细胞因子并没有显著改变疾病的发生率，潜在地表明细胞因子反应中存在冗余。因此，这些结果表征了C57BL/6J小鼠斑秃的新的高发模型，首次应用了单克隆性TCR，并表明I类MHC限制性CD8+T淋巴细胞可以独立地介导病理反应。
Alopecia areata is among the most prevalent autoimmune diseases, yet compared with other autoimmune conditions is not well studied. This in part results from limitations in the C3H/HeJ mouse and DEBR rat model systems most commonly used to study the disease, which display a low frequency and late onset. We describe a novel high incidence model for spontaneous alopecia areata. The 1MOG244 T cell expresses dual TCRA chains, one of which, when combined with the single TCRB present, promotes the development of CD8+ T cells with specificity for hair follicles. Retroviral transgenic mice expressing this TCR develop spontaneous alopecia areata at nearly 100% incidence. Disease initially follows a reticular pattern, with regionally cyclic episodes of hair loss and regrowth, and ultimately progresses to alopecia universalis. Alopecia development is associated with CD8+ T cell activation, migration into the intrafollicular region, and hair follicle destruction. The disease may be adoptively transferred with T lymphocytes, and is class I and not class II MHC-dependent. Pathologic T cells primarily express IFNG and IL17 early in disease, with dramatic increases in cytokine production and recruitment of IL4 and IL10 production with disease progression. Inhibition of individual cytokines did not significantly alter disease incidence, potentially indicating redundancy in cytokine responses. These results therefore characterize a new high incidence model for alopecia areata in C57BL/6J mice, the first to apply a monoclonal TCR, and indicate that class I MHC-restricted CD8+ T lymphocytes can independently mediate the pathologic response.
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影响因子：
13.8
作者：
Barahmani, Nazila;Schabath, Matthew B.;Duvic, Madeleine
通讯作者：
Duvic, Madeleine
影响因子：
--
作者：
Gilhar, A;Landau, M;Kalish, RS
通讯作者：
Kalish, RS
病毒感染通过激活表达双重 TCR 的 CD8+ T 细胞触发中枢神经系统自身免疫。
影响因子：
30.5
作者：
Ji, Qingyong;Perchellet, Antoine;Goverman, Joan M.
通讯作者：
Goverman, Joan M.
DOI：
10.1111/j.0022-202x.2005.10130_5.x
发表时间：
2005-12-01
期刊：
The journal of investigative dermatology. Symposium proceedings
影响因子：
--
作者：
Freyschmidt-Paul, P;Zoller, M;Hoffmann, R
通讯作者：
Hoffmann, R
影响因子：
4.4
作者：
Bozza, Silvia;Zelante, Teresa;Romani, Luigina
通讯作者：
Romani, Luigina