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T Cell Requirement for Development of Chronic Ulcerative Dermatitis in E- and P-Selectin-Deficient Mice¹

S. Bradley Forlow^*,, E. James White^*, Kennard L. Thomas^*,, Gregory J. Bagby^¶, Patricia L. Foley and Klaus Ley^2,*,

^* Department of Biomedical Engineering, Cardiovascular Research Center, and Center for Comparative Medicine, University of Virginia, Charlottesville, VA 22908; Center for Blood Research, Harvard Medical School, Boston, MA 02115; and ^¶ Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA 70112

C57BL/6 mice deficient in E- and P-selectin (E^-/-P^-/-) kept under specific pathogen-free barrier conditions have high circulating neutrophil counts and develop hypercellular cervical lymph nodes with substantial plasma cell infiltrates, severe ulcerative dermatitis, conjunctivitis, and lung pathology, which eventually lead to premature death. To test the hypothesis that the pathology in E^-/-P^-/- mice may be caused by dysfunctional lymphocyte activity, we crossed E^-/-P^-/- mice with recombination activation gene (Rag)-1^-/- mice to generate E^-/-P^-/-Rag-1^-/- mice lacking mature T and B lymphocytes. E^-/-P^-/-Rag-1^-/- mice had circulating neutrophil counts and plasma G-CSF levels similar to E^-/-P^-/- mice. Remarkably, none of the E^-/-P^-/-Rag-1^-/- mice developed conjunctivitis or ulcerative dermatitis typical of E^-/-P^-/- mice. These mice were overall healthier in appearance than E^-/-P^-/- mice, and histopathologic changes in the lung were reduced. Cervical lymph nodes in E^-/-P^-/-Rag-1^-/- mice were much smaller than those of E^-/-P^-/- mice, containing few mononuclear cells and no plasma cells. These data show that the severe disease phenotype of E^-/-P^-/- mice depends on lymphocyte function. We conclude that a dysregulated immune response in E^-/-P^-/- mice causes disease development, but is not necessary for elevated neutrophil counts.

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