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.

journal_name

Int Immunol

journal_title

International immunology

authors

Barlow SC,Xu H,Weaver CT,Lindsey JR,Schoeb TR,Bullard DC

doi

10.1093/intimm/dxh028

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

345-51

issue

2

eissn

0953-8178

issn

1460-2377

journal_volume

16

pub_type

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