CD4 super(+) T Cell-Associated Pathophysiology Critically Depends on CD18 Gene Dose Effects in a Murine Model of Psoriasis

• Published in: The Journal of immunology (1950) Vol. 171; no. 11; pp. 5697 - 5706
• Main Authors: Kess, D, Peters, T, Zamek, J, Wickenhauser, C, Tawadros, S, Loser, K, Varga, G, Grabbe, S, Nischt, R, Sunderkoetter, C, Mueller, W, Krieg, T, Scharffetter-Kochanek, K
• Format: Journal Article
• Language: English
• Published: 01-01-2003
• ISSN: 0022-1767

In a CD18 hypomorphic polygenic PL/J mouse model, the severe reduction of CD18 ( beta sub(2) integrin) to 2-16% of wild-type levels leads to the development of a psoriasiform skin disease. In this study, we analyzed the influence of reduced CD18 gene expression on T cell function, and its contribution to the pathogenesis of this disease. Both CD4 super(+) and CD8 super(+) T cells were significantly increased in the skin of affected CD18 hypomorphic mice. But only depletion of CD4 super(+) T cells, and not the removal of CD8 super(+) T cells, resulted in a complete clearance of the psoriasiform dermatitis. This indicates a central role of CD4 super(+) T cells in the pathogenesis of this disorder, further supported by the detection of several Th1-like cytokines released predominantly by CD4 super(+) T cells. In contrast to the CD18 hypomorphic mice, CD18 null mutants of the same strain did not develop the psoriasiform dermatitis. This is in part due to a lack of T cell emigration from dermal blood vessels, as experimental allergic contact dermatitis could be induced in CD18 hypomorphic and wild-type mice, but not in CD18 null mutants. Hence, 2-16% of CD18 gene expression is obviously sufficient for T cell emigration driving the inflammatory phenotype in CD18 hypomorphic mice. Our data suggest that the pathogenic involvement of CD4 super(+) T cells depends on a gene dose effect with a reduced expression of the CD18 protein in PL/J mice. This murine inflammatory skin model may also have relevance for human polygenic inflammatory diseases.