RESEARCH - Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection

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J Immunol. 2009 Jan 1;182(1):309-18.

Antibodies to MHC class I induce autoimmunity: role in the

pathogenesis of chronic rejection.

Fukami N, Ramachandran S, Saini D, Walter M, Chapman W, GA,

Mohanakumar T.

Department of Surgery.

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-alpha1 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.

PMID: 19109162

http://www.ncbi.nlm.nih.gov/pubmed/19109162

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