Antibodies to MHC class I induce autoimmunity: Role in the pathogenesis of chronic rejection

Naohiko Fukami, Sabarinathan Ramachandran, Deepti Saini, Michael Walter, William Chapman, G. Alexander Patterson, Thalachallour Mohanakumar

研究成果: Article査読

138 被引用数 (Scopus)

抄録

Alloimmunity to mismatched donor HLA-Ags and autoimmunity to self-Ags have been hypothesized to play an important role in immunopathogenesis of chronic rejection of transplanted organs. However, it is not known what role, if any, alloimmune response plays in inducing autoimmunity. To test whether Ab-developed posttransplantation to mismatched donor MHC induces autoimmunity and chronic rejection, we developed a murine model wherein anti-MHC class I Abs or control (C1.18.4/anti-keratin) were administered intrabronchially into native lungs. Animals receiving anti-MHC class I, but not control Abs, developed marked cellular infiltration around vessels and bronchiole of lung by day 15, followed by epithelial hyperplasia, fibrosis, and occlusion of the distal airways similar to chronic rejection following human lung transplantation. Lungs of mice receiving anti-MHC class I showed increased expression of chemokines, their receptors, and growth factors, and induced IL-17 as well as de novo Abs to self-Ags, K-α1 tubulin, and collagen V. IL-17 neutralization by anti-IL-17 resulted in reduction of autoantibody and lesions induced by anti-MHC class I Abs. Thus, our results indicate that Abs to donor MHC can induce autoimmunity, mediated by IL-17, which plays a pivotal role in chronic rejection postlung transplantation. Therefore, approaches to prevent autoimmunity should be considered for the treatment of chronic rejection postlung transplantation.

本文言語English
ページ(範囲)309-318
ページ数10
ジャーナルJournal of Immunology
182
1
DOI
出版ステータスPublished - 01-01-2009

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学

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