title: A mouse model of clonal CD8+ T lymphocyte-mediated alopecia areata progressing to alopecia universalis.
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.
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Rajshekhar
authors: R
authors: Alli
authors: Phuong
authors: P
authors: Nguyen
authors: Kelli
authors: K
authors: Boyd
authors: John P
authors: JP
authors: Sundberg
authors: Terrence L
authors: TL
authors: Geiger
mesh_terms: D000506:Alopecia Areata / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018859:Hair Follicle / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C556062:IL10 protein, mouse; D020381:Interleukin-17; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10; D015847:Interleukin-4