A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis.

Alli R, Nguyen P, Boyd K, Sundberg JP, Geiger TL
J Immunol. 2012 188 (1): 477-86

PMID: 22116824 · PMCID: PMC3244525 · DOI:10.4049/jimmunol.1100657

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.

MeSH Terms (15)

Alopecia Areata Animals CD8-Positive T-Lymphocytes Hair Follicle Histocompatibility Antigens Class I Histocompatibility Antigens Class II Humans Interleukin-4 Interleukin-10 Interleukin-17 Lymphocyte Activation Mice Mice, Knockout Rats Receptors, Antigen, T-Cell, alpha-beta

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