Partial restoration of hair growth in the DEBR model for alopecia areata afterin vivodepletion of CD4+ T cells

Abstract

Alopecia areata (AA) is widely believed to be an autoimmune disease. Hair loss is associated with a peri- and intrafollicular inflammatory infiltrate of anagen hair follicles primarily composed of CD4 + and CD8 + cells. A previous investigation involved in vivo depletion of CD8 + cells in the DEBR rat model to examine the cells' potential pathogenic activity in AA. The rat model is used here in a comparable study of CD4 + cell pathogenic activity. Eight AA affected DEBR rats were given intraperitoneal injections of a CD4 + cell depleting OX-35/OX-38 monoclonal antibody (MoAb) cocktail over a 15-day therapy course. A further eight AA-affected rats comprised a control group and were injected with equivalent volumes of an irrelevant MoAb, OX-21. Changes in both CD4 + and CD8 + peripheral blood cell populations were analysed by flow cytometry, and macrophotography was used to record any changes in hair growth. Of the eight CD4 + cell-depleted rats six responded with hair growth. The rats revealed significant hair growth within 23 days of treatment initiation. With rapid replacement of the CD4 + cell population the newly generated pelage hair was eventually lost. Two control rats also showed limited hair growth within the 112-day study period. In vivo depletion of CD4 + cells partially restores hair growth in AA affected rats. The response suggests that CD4 + cells may be actively involved in the pathogenesis of AA. Further research may elucidate whether CD4 + cells have a direct effect on hair follicles or exert their influence through their classic T helper cell supporting role for CD8 + cells.

Lymphocytes, neuropeptides, and genes involved in alopecia areata

“…The DEBR rat is another well established animal model of a spontaneously arising disease that is similar to AA (73,74). Depletion of either CD8 + or CD4 + T cells results in complete hair regrowth in this rat model (75,76).…”

Phase I/II randomized bilateral half-head comparison of topical bexarotene 1% gel for alopecia areata

“…5 In animal models, depletion of either activated CD8 1 or CD4 1 T cells restores hair growth. 6 Thus, a T-celledirected therapeutic approach should restore hair growth in human AA.…”

The role of lymphocytes in the development and treatment of alopecia areata

“…By microarray analyses, several key effector CTL specific transcripts have been identified in mouse and human AA skin [16]. Depletion of CD4 + or CD8 + cells using monoclonal antibodies (mAb) enables hair regrowth in mouse and rat models [83][84][85]. Transfer of CD8 + T cells in conjunction with CD4 + T cells can induce extensive AA lesions in mouse models [16,77,[86][87][88].…”