Development of dermatitis in CD18‐deficient PL/J mice is not dependent on bacterial flora, and requires both CD4+ and CD8+ T lymphocytes

CD18-deficient PUJ mice develop dermatitis characterized by hyperkeratosis, and a mixed dermal and epidermal inflammatory infiltrate. The development of this disease requires low-level CD18 expression and at least two PUJloci. Currently, the mechanisms by which decreased β 2 integrin expression on leukocytes promotes skin inflammation in PUJ mice are unknown. In these studies, we investigated the role of microbial infection and T lymphocytes in the pathogenesis of this disease. We found that germ-free CD18 - / - PUJ mice developed dermatitis indistinguishable from that of mice raised in pathogen-free conditions. Adoptive transfer of CD18 - / - PUJ splenocytes into skin disease-resistant CD18 + / - PUJ mice failed to induce skin inflammation. However, transfer of CD18 + / - splenocytes blocked the progression and ultimately led to resolution of skin disease in the majority of CD18 - / - recipients. Depletion of both CD4 + and CD8 + T cells mice prior to onset of the disease significantly delayed the appearance of inflammatory skin disease. In contrast, single depletions of these T cells did not inhibit disease development. These studies show that dermatitis in CD18-deficient PUJ mice is not the consequence of infection, does not require bacterial superantigens, and is mediated by both CD4 + and CD8 + T lymphocytes. Furthermore, they suggest that one possible mechanism for skin disease development in these mice may involve the absence or dysfunctional activity of a regulatory T cell population. These mice may therefore be useful In identifying potential mechanisms of pathogenesis and genetic predisposition in human Inflammatory skin diseases.