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

• Published in: International immunology Vol. 16; no. 2; pp. 345 - 351
• Main Authors: Barlow, Shayne C., Xu, Hui, Weaver, Casey T., Lindsey, J. Russell, Schoeb, Trenton R., Bullard, Daniel C.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-02-2004; Oxford Publishing Limited (England)
• Subjects: adhesion molecule; Adoptive Transfer; Animals; Bacterial Infections - etiology; Bacterial Infections - genetics; Bacterial Infections - immunology; Bacterial Infections - therapy; CD18; CD18 Antigens - genetics; CD18 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Dermatitis - genetics; Dermatitis - immunology; Dermatitis - microbiology; Dermatitis - prevention & control; germ‐free; Humans; Lymphocyte Activation - immunology; Mice; Mice, Knockout; psoriasis; Superantigens - immunology; T lymphocyte
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxh028

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 β2 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.