title: Role of alloimmunity and autoimmunity in allograft rejection.
abstract: Pathophysiology of chronic rejection strongly supports that inflammation and subsequent tissue remodeling during the post-transplant period cause exposure of cryptic self-antigens (SAgs) or their determinants within the graft, which, along with a subsequent cytokine response, leads to loss of peripheral tolerance. These events lead to the activation of cell-mediated immunity towards development of de novo immune responses to SAgs. There is also evidence for a role for interplay between allo- and autoimmunity in the development of chronic rejection. Experimental results using murine models of Obliterative Airway Disease (OAD) akin to chronic lung allograft rejection have clearly demonstrated that autoimmune responses to Collagen V (ColV) and K-alpha 1 Tubulin (KalT) were induced by administration of antibodies (Abs) against class I major histocompatibility complex antigens. Further, inhibition of interleukin (IL)-17 abrogated the autoimmune response and development of OAD. This shows an important relationship between alloimmunity, autoimmunity to SAgs such as KalT, and a significant role for IL-17 pathway of immune activation. Recent reports demonstrate that in addition to lung transplant recipients, kidney transplant recipients diagnosed with transplant glomerulopathy can develop de novo Abs to Sags, including Col-IV and fibronectin and heart transplant recipients can develop immune responses to cardiac myosin and vimentin. Abs to SAgs were identified frequently with donor specific anti-human leukocyte antigen antibodies, supporting the concept of crosstalk between auto- and alloimmunity. The increased frequency of SAg specific interferon-gamma and IL-17 cells with reduction in IL-10 demonstrates tolerance breakdown to SAgs which may play a significant role in the pathogenesis of chronic rejection.
authors.forename: Babak
authors.initials: B
authors.lastname: Banan
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Xu
authors.forename: Muthukumar
authors.initials: M
authors.lastname: Gunasekaran
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D014184:Transplantation, Homologous
chemical_list: D001323:Autoantibodies; D007518:Isoantibodies
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