Treatment with an anti-CD44v10-specific antibody inhibits the onset of alopecia areata in C3H/HeJ mice.
A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8+ lymphocytes and, to a lesser degree, CD4+ cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8+ T cells), resulting in a decrease of their number in target tissues.
Freyschmidt-Paul
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Department of Dermatology and the Institute of Medical Biometry and Epidemiology, Philipp University, Marburg, Germany. freyschm@mailer.uni-marburg.de
Seiter
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Zöller
M
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König
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Ziegler
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Sundberg
J P
JP
Happle
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Hoffmann
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D000506:Alopecia Areata / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D012867:Skin / Q000187:drug effects / Q000473:pathology
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors