Antibodies to MHC Class II Molecules Induce Autoimmunity: Critical Role for Macrophages in the Immunopathogenesis of Obliterative Airway Disease

作者：Takenaka Masashi^*; Tiriveedhi Venkataswarup; Subramanian Vijay; Hoshinaga Kiyotaka; Patterson Alexander G; Mohanakumar Thalachallour

来源：PLos One, 2012, 7(8): e42370.

DOI：10.1371/journal.pone.0042370

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- alpha 1Tubulin). Further, lung-infiltrating macrophages demonstrated a switch in their phenotype predominance from M Phi 1 (F4/80(+)CD11c(+)) to M Phi 2 (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 naive animals induced OAD lesions. We conclude that MHC class II Abs induces a phenotype switch of lung infiltrating macrophages from M Phi 1 (F4/80(+)CD11c(+)) to M Phi 2 (F4/80(+)CD206(+)) resulting in the breakdown of self-tolerance along with an increase in autoimmune Th17 response leading to OAD.

• 出版日期2012-8-10