期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 12, 期 4, 页码 867-876出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-6143.2011.03917.x
关键词
Autoimmunity; anti-MHC; antibodies; B-cell; cytokines; IL-17; OAD
资金
- NIH [HL092514]
- BJC Foundation
Using a murine model, we demonstrated that endobronchial administration of antibodies (Abs) to major histocompatibility complex (MHC) class I results in cellular infiltration, epithelial metaplasia, fibrosis and obstruction of the small airways (obliterative airway disease [OAD]) mediated predominantly by Th17 responses to self-antigens. This resembles bronchiolitis obliterans syndrome developed following human lung transplantation. Since B cells play a crucial role in induction of autoimmune responses, we defined the role of B cells and its antigen presenting properties in induction of OAD in this study. Anti-MHC class I was administered endobronchially in B-/- and wild-type mice. In contrast to wild type, B-/- animals did not demonstrate cellular infiltration, epithelial metaplasia and obstruction of airways following anti-MHC. Frequency of K-a1 tubulin and CollagenV-specific IL-17 cells was significantly decreased in B-/- mice. As expected, Abs against self-antigens and germinal center formation were not developed in B-/- mice. Thus, we conclude that B cells and its antigen presenting capacity play an important role in induction of immune responses to self-antigens and immunopathogenesis of OAD following the administration of anti-MHC. Therefore, strategies to block B-cell and its antigen presenting functions should be considered for preventing the development of chronic rejection.
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