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Immunology - Respiratory Medicine - Surgery

Antibodies to MHC Class II Molecules Induce Autoimmunity: Critical Role for Macrophages in the Immunopathogenesis of Obliterative Airway Disease
Published: Friday, August 10, 2012
Author: Masashi Takenaka et al.

by Masashi Takenaka, Venkataswarup Tiriveedhi, Vijay Subramanian, Kiyotaka Hoshinaga, Alexander G. Patterson, Thalachallour Mohanakumar

Previous studies have shown that intrabronchial administration of antibodies (Abs) to MHC class I resulted in development of obliterative airway disease (OAD), a correlate of chronic human lung allograft rejection. Since development of Abs specific to mismatched donor HLA class II have also been associated with chronic human lung allograft rejection, we analyzed the role of Abs to MHC class II in inducing OAD. Administration of MHC class II Abs (M5/114) to C57BL/6 mice induced the classical features of OAD even though MHC class II expression is absent de novo on murine lung epithelial and endothelial cells. The induction of OAD was accompanied by enhanced cellular and humoral immune responses to self-antigens (Collagen V and K- a1Tubulin). Further, lung-infiltrating macrophages demonstrated a switch in their phenotype predominance from MF1 (F4/80+CD11c+) to MF2 (F4/80+CD206+) following administration of Abs and prior to development of OAD. Passive administration of macrophages harvested from animals with OAD but not from naïve animals induced OAD lesions. We conclude that MHC class II Abs induces a phenotype switch of lung infiltrating macrophages from MF1 (F4/80+CD11c+) to MF2 (F4/80+CD206+) resulting in the breakdown of self-tolerance along with an increase in autoimmune Th17 response leading to OAD.