Barlow Shayne C, Xu Hui, Weaver Casey T, Lindsey J Russell, Schoeb Trenton R, Bullard Daniel C
Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Int Immunol. 2004 Feb;16(2):345-51. 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 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.
CD18缺陷的PL/J小鼠会发生以角化过度为特征的皮炎，并伴有真皮和表皮混合性炎性浸润。这种疾病的发生需要低水平的CD18表达以及至少两个PL/J基因座。目前，白细胞上β(2)整合素表达降低促进PL/J小鼠皮肤炎症的机制尚不清楚。在这些研究中，我们调查了微生物感染和T淋巴细胞在该疾病发病机制中的作用。我们发现无菌的CD18(-/-) PL/J小鼠发生的皮炎与在无病原体条件下饲养的小鼠的皮炎无法区分。将CD18(-/-) PL/J脾细胞过继转移到抗皮肤疾病的CD18(+/-) PL/J小鼠中未能诱导皮肤炎症。然而，转移CD18(+/-)脾细胞可阻止疾病进展，并最终导致大多数CD18(-/-)受体的皮肤疾病消退。在疾病发作前耗尽CD4(+)和CD8(+) T细胞小鼠显著延迟了炎性皮肤疾病的出现。相比之下，单独耗尽这些T细胞并不抑制疾病发展。这些研究表明，CD18缺陷的PL/J小鼠中的皮炎不是感染的结果，不需要细菌超抗原，并且由CD4(+)和CD8(+) T淋巴细胞介导。此外，它们表明这些小鼠皮肤疾病发生的一种可能机制可能涉及调节性T细胞群体的缺失或功能失调。因此，这些小鼠可能有助于确定人类炎性皮肤疾病发病机制和遗传易感性的潜在机制。
