1. ^*Division of Dermatology, University of British Columbia, Vancouver, BC, Canada
2. ^†Department of Dermatology, Philipp University, Marburg, Germany
3. ^‡Department of Dermatology, Albert-Ludwigs-University, Freiburg, Germany
4. ^§Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg, Germany

Correspondence: Kevin J. McElwee, Division of Dermatology, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, Canada. Emails: kevin@keratin.com, kmcelwee@interchange.ubc.ca

¹These authors contributed equally to this work.

Received 27 May 2004; Revised 1 December 2004; Accepted 13 December 2004.

Abstract

Alopecia areata (AA) is a suspected hair follicle specific autoimmune disease. The potential for cell transfer of AA using the C3H/HeJ mouse model was examined. Cells isolated from lymph nodes and spleens of AA-affected mice using magnetic bead conjugated monoclonal antibodies were subcutaneously injected into normal C3H/HeJ recipients. Within 5 wk, all CD8⁺ cell-injected mice exhibited localized hair loss exclusively at the site of injection that persisted until necropsy. In contrast, some CD4⁺ and CD4⁺/CD25^- cell-injected mice developed extensive, systemic AA, and a combination of CD8⁺ and CD4⁺/CD25^- cells injected yielded the highest frequency of systemic AA induction. CD4⁺/CD25⁺ cells were less able to transfer the disease phenotype, partially blockaded systemic AA induction by CD4⁺/CD25^- cells, and prevented CD8⁺ cell-induced, injection site-localized hair loss. CD11c⁺ and CD19⁺ cells failed to promote significant phenotype changes. Increases in co-stimulatory ligands CD40 and CD80, plus increased leukocyte apoptosis resistance with reduced CD95, CD95L, and CD120b expression, were associated with successful alopecia induction. The results suggest that CD8⁺ cells may be the primary instigators of the hair loss phenotype. However, systemic disease expression fate is, apparently determined by CD4⁺/CD25^- cells, while CD4⁺/CD25⁺ lymphocytes may play a predominantly regulatory role.