title: Development of dermatitis in CD18-deficient PL/J mice is not dependent on bacterial flora, and requires both CD4+ and CD8+ T lymphocytes.
abstract: 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 beta(2) 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.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Shayne C
authors.initials: SC
authors.lastname: Barlow
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.forename: J Russell
authors.initials: JR
authors.lastname: Lindsey
authors.forename: Trenton R
authors.initials: TR
authors.lastname: Schoeb
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000628:therapy; D018821:CD18 Antigens / Q000235:genetics* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003872:Dermatitis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D018089:Superantigens / Q000276:immunology
chemical_list: D018821:CD18 Antigens; D018089:Superantigens