International Immunology, Vol. 16, No. 2, pp. 345-351,
February 2004
© 2004 Japanese Society for Immunology
Development of dermatitis in CD18-deficient PL/J mice is not dependent on bacterial flora, and requires both CD4+ and CD8+ T lymphocytes
Departments of 1 Genetics, 2 Dermatology and 3 Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Correspondence to: D. Bullard; E-mail: pike{at}uab.edu
Transmitting editor: T. Tedder
CD18-deficient PL/J 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 PL/J loci. Currently, the mechanisms by which decreased ß2 integrin expression on leukocytes promotes skin inflammation in PL/J 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–/– PL/J mice developed dermatitis indistinguishable from that of mice raised in pathogen-free conditions. Adoptive transfer of CD18–/– PL/J splenocytes into skin disease-resistant CD18+/– PL/J 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 PL/J 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.
Keywords: adhesion molecule, CD18, germ-free, psoriasis, T lymphocyte
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