L9 WHAT CAN WE LEARN FROM ANIMAL MODELS OF ALOPECIA AREATA?
McElwee K, Shapiro J
Department of Dermatology, University of British Columbia, Vancouver, B.C., Canada

Alopecia areata (AA) is a suspected autoimmune disease where hair loss is associated with an inflammatory infiltrate comprised of CD4+ and CD8+ lymphocytes, focused on anagen stage hair follicles. The functional evidence to prove AA is truly an autoimmune disease is not complete and the characterisation of the primary pathogenic mechanisms by which hair loss is induced is still quite limited. In practice, the studies required to provide fundamental evidence of the autoimmune disease mechanism in AA may never be conducted on humans given the ethical limitations of human experimentation. Animal models provide a practical alternative. Koch's postulates, as adapted to autoimmune disease, enable a classification of evidence into circumstantial, indirect, and direct proof of autoimmunity. Considerable circumstantial evidence is available from both humans and animal models and indirect evidence in support of an autoimmune pathogenesis is accumulating. Direct evidence in support of AA as a true autoimmune disease essentially comprises; 1) induction of disease by autoreactive lymphocytes and/or antibodies by transfer from affected to unaffected individuals, 2) identification of primary pathogenic self antigen(s) in the disease initiating event, and 3) induction of disease by immunization of naive recipients with target epitope antigen(s) or anti-idiotype antibodies. Recent animal model research has focused on disease transfer using activated leukocytes. Leukocytes isolated from AA affected C3H/HeJ mice using magnetic bead conjugated monoclonal antibodies were subcutaneously injected into normal recipients. Within 5 weeks, 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. The results suggest CD8+ cells may be the primary instigators of the hair loss phenotype while systemic disease expression fate is determined by CD4+/CD25- cells and CD4+/CD25+ lymphocytes play a predominantly regulatory role. These and other studies help to confirm the first of Koch's postulates and prove AA as an autoimmune disease. In the near future, AA research with both humans and animal models shall concentrate on identifying the primary antigenic epitopes involved in AA. With a comprehensive understanding of the key elements in AA pathogenesis, so new avenues for therapeutic research will be defined.