Treatment of Alopecia Areata with Anti-Interferon-γ Antibodies

Abstract

Our data show that IFN-g / mice are resistant to the development of AA, pointing toward an important role of IFN-g in the pathogenesis of AA. The absence of a perifollicular lymphocytic infiltrate in the skin and the reduced expression of T cell activation markers and costimulatory molecules in skin-draining lymph nodes demonstrate that T cells are not activated in the lymph nodes of IFN-g / mice. Therefore, we conclude that IFN-g is involved in T cell activation in AA pathogenesis of C3H/ HeJ mice. A pathogenetic role for IL-2 in AA could also be demonstrated, but the cogency of our data is limited because only heterozygous IL-2þ / mice were available for these experiments. But Hollander et al (Science 1998) demonstrated that IL-2 expression is reduced 50% in IL2þ / mice compared with IL-2þ /þ mice. Our data show that the frequency of AA development is significantly reduced in IL-2þ / mice. Therefore, we conclude that the magnitude of IL-2 expression influences the frequency of AA development. FACS analysis and immunohistochemistry show that AA resistance of half of the IL-2þ / mice is related to a reduced T cell activation in the lymph nodes and an absence of perifollicular infiltrates of CD4þ and CD8þ cells in the skin. These data suggest that AA development in the C3H/HeJ mouse model depends on the level of IL-2 expression and on subsequent T cell activation in the lymph nodes. Taken together, our results show that the type-1 cytokines IFN-g and IL-2 are involved in T cell activation in the development of AA in the C3H/HeJ mouse model.