Abstract |
Alopecia areata is among the most prevalent autoimmune diseases, yet compared with other autoimmune conditions, it 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 IL-17 early in disease, with dramatic increases in cytokine production and recruitment of IL-4 and IL-10 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 our knowledge 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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Authors | Rajshekhar Alli, Phuong Nguyen, Kelli Boyd, John P Sundberg, Terrence L Geiger |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 188
Issue 1
Pg. 477-86
(Jan 01 2012)
ISSN: 1550-6606 [Electronic] United States |
PMID | 22116824
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Histocompatibility Antigens Class I
- Histocompatibility Antigens Class II
- IL10 protein, mouse
- Interleukin-17
- Receptors, Antigen, T-Cell, alpha-beta
- Interleukin-10
- Interleukin-4
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Topics |
- Alopecia Areata
(genetics, immunology, pathology)
- Animals
- CD8-Positive T-Lymphocytes
(immunology, pathology)
- Hair Follicle
(immunology, pathology)
- Histocompatibility Antigens Class I
(genetics, immunology)
- Histocompatibility Antigens Class II
(genetics, immunology)
- Humans
- Interleukin-10
(genetics, immunology)
- Interleukin-17
(genetics, immunology)
- Interleukin-4
(genetics, immunology)
- Lymphocyte Activation
(genetics, immunology)
- Mice
- Mice, Knockout
- Rats
- Receptors, Antigen, T-Cell, alpha-beta
(genetics, immunology)
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