Alloimmunity induced autoimmunity: Role in the pathogenesis of chronic allograft rejection

Tremendous progress has been made in the field of transplantation with significant improvement in preventing acute rejection that has resulted in improved graft survival. However long term graft survival still remains limited due to chronic allograft rejection. Chronic rejection is a major impediment for long-term graft function and its incidence is almost universal especially following human lung transplantation. Alloimmune responses to mismatched major histocompatibility antigens (MHC) have been implicated as the most important process leading to rejection. However there is increasing evidence for cross talk between the immune responses to infection, peri-operative inflammation and autoimmunity with allo-immune responses in the transplanted organ leading to chronic rejection. The role of autoimmunity in the development of chronic rejection has been an exciting avenue with significant potential to develop novel strategies in the future to prevent chronic allograft rejection. In this review, we will discuss studies and the emerging concept of the role of autoimmunity and the cross talk between alloimmune and autoimmune responses in the development of chronic allograft rejection, with special emphasis on chronic rejection following human lung transplantation – clinically diagnosed as Bronchiolitis Obliterans Syndrome (BOS). We will provide an important role for Th17 cells, regulatory T cells (Tregs) and immune responses to self-antigens expressed in lung parenchyma in the immunopathogenesis of BOS.