A Mouse Model of Clonal CD8+ T Lymphocyte-Mediated Alopecia Areata Progressing to Alopecia Universalis
Rajshekhar Alli*, Phuong Nguyen*, Kelli Boyd*,†, John P. Sundberg‡ and Terrence L. Geiger*
+ Author Affiliations
*Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105;
†Department of Pathology, Vanderbilt University, Nashville, TN 37232; and
‡The Jackson Laboratory, Bar Harbor, ME 04609
Address correspondence and reprint requests to Dr. Terrence L. Geiger, Department of Pathology, St. Jude Children’s Research Hospital, 262 St. Jude Place, D-4047, Memphis, TN 38105. E-mail address: email@example.com
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.
This work was supported by National Institutes of Health Grants R01 AI056153 (to T.L.G.) and R01 AR056635 (to J.P.S.), the American Lebanese Syrian Associated Charities/St. Jude Children’s Research Hospital (to R.A., P.N., K.B., and T.L.G.), and the North American Hair Research Society (to K.B.).
The online version of this article contains supplemental material.
Received March 8, 2011.
Accepted October 22, 2011.
Copyright © 2011 by The American Association of Immunologists This is the all text and i copy and past it all as it was now i don't really get the text because all the scientific words, what does retroviral transgenic mice even mean?? Does it mean a mice that had retrovirus and that passed it to the other mice?Sadly i think they mean that, am not sure did look up some retroviruses if this is the case they are contagious and remain in body for life cause all kind of problems and even breast cancer that i didn't even know was a cause from virus and leukemia to now seems for alopecia as well..