Abstract
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-α 1 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.
Original language | English (US) |
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Pages (from-to) | 867-876 |
Number of pages | 10 |
Journal | American Journal of Transplantation |
Volume | 12 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2012 |
Keywords
- Anti-MHC
- Antibodies
- Autoimmunity
- B-cell
- Cytokines
- IL-17
- OAD