Autoantibody formation in human and rat studies of chronic rejection and primary graft dysfunction
Lung transplantation is considered a definitive treatment for many lung diseases. However, rejection and other pathologic entities are major causes of morbidity and mortality for lung transplant recipients. Primary graft dysfunction (PGD) and obliterative bronchiolitis (OB) are the leading causes of early and late mortality, respectively. While the immune basis of PGD has not been clearly defined, evidence is emerging about roles for autoantibodies in this process. Similarly, the pathogenesis of OB has been linked recently to autoimmunity. This review will highlight the current understanding of autoantibodies in PGD and OB post lung transplantation.
- [Show abstract] [Hide abstract] ABSTRACT: Purpose of review: To discuss the B-cell diverse functions in organ transplantation, highlighting the emerging debate on the role of regulatory B cells (Bregs). We underscore the need to re-examine and integrate data on B-cell functional activities, aiming to discriminate their regulatory (REG) and inflammatory (INFLAMMA) functions and to translate this knowledge for the development of novel immunomodulatory therapeutic strategies and to rethink the current ones. Recent findings: Data from both experimental models and clinical trials point that B cells of various phenotypes have immunoregulatory activity and play an important role in controlling graft inflammation. Data on the state of operational tolerance, in kidney transplantation, suggest the relevance of preserving a healthy B-cell compartment - in numbers and in the Breg capacity to activate the CD40/STAT3 signalling pathway - for achieving and maintaining homeostasis. Moreover, autoantibodies also comprise transplant immunobiology and it seems that not all alloantibodies are deleterious. Summary: The role of B cells, in organ transplantation, can no longer be taken as mere generators of plasma cells, which produce alloantibodies deleterious to the graft. B cells also seem to integrate a complex immunoregulatory network in organ transplantation, with Bregs of various phenotypes and possibly also antibodies. The functional discrimination of REG/INFLAMMA B-cell roles needs to be considered in the clinical setting.
- [Show abstract] [Hide abstract] ABSTRACT: The identification of T-helper 9 (Th9), Th17, Th22 cells as distinct subsets of CD4(+) T cells has extended the Th1/Th2 paradigm in the adaptive immunity. In the past decade, many studies in animal models and clinical transplantation have demonstrated that interleukin-17 (IL-17) is involved in allograft rejection. It appears that Th17 cells together with Th1 and Th2 cells play an important role in mediating allograft rejection. Here, we summarize our current knowledge on the contribution of Th1, Th2, Th9, Th17, Th22, and follicular T-helper (Tfh) cells in allograft rejection. We also discuss the regulation of CD4(+) T-cell subsets by CD4(+) Foxp3(+) regulatory T cells (Tregs) in the context of transplantation tolerance.