Humoral Immunity and Development of Obliterative Bronchiolitis Post Lung Transplantation - is there a Link?
ABSTRACT Lung transplantation is considered a definitive treatment for many end stage lung diseases. However, the lung is rejected more commonly than other solid organ allografts. Obliterative bronchiolitis (OB) is the leading cause of chronic allograft dysfunction and the key reason why five year survival of lung transplant recipient is only 50%. The pathophysiology of OB is incompletely understood. While there is a clear role for immune response to donor antigens, also known as anti- human leukocyte antigens (anti-HLA), evidence is emerging about the role of autoimmunity to self antigens. This review will highlight the current understanding of humoral immunity in development of OB post lung transplantation.
Article: Lessons and Limits of Mouse Models[Show abstract] [Hide abstract]
ABSTRACT: Seminal studies in rabbits and rodent transplantation models by Peter Medawar revealed that cellular processes, rather than humoral antibodies, are central to the acute rejection of transplanted organs, and much of basic transplantation research continues to be focused on the biology and control of these cells, which were subsequently shown to be T cells. However, the success of current immunosuppression at controlling T-cell-mediated rejection has resulted in an increasing awareness of antibody-mediated rejection in the clinic. This, in turn, has fueled an emerging interest in the biology of allospecific antibodies, the B cells that produce these antibodies, and the development of mouse models that allow their investigation. Here we summarize some of the more widely used mouse models that have been developed to study the immunobiology of alloreactivity, transplantation rejection and tolerance, and used to identify therapeutic strategies that modulate these events.Cold Spring Harbor Perspectives in Medicine 12/2013; 3(12). DOI:10.1101/cshperspect.a015495 · 7.56 Impact Factor
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ABSTRACT: This study aimed to investigate the role of inducible costimulatory molecule (ICOS) pathway in the rejection reaction of mice undergoing allogeneic tracheal transplantation. The bronchus was separated from wide-type (WT) BalB/c mice and transplanted into WT BalB/c mice, C57 mice and icos(-/-) mice to prepare the obliterative bronchiolitis (OB) animal model. The transplanted bronchus was pathologically examined; flow cytometry was done to detect the T cell subsets and activity of the bronchus and spleen of recipient mice. 21 d after transplantation, evident rejection reaction was observed and the proportion of Th2 and Th17 cells increased significantly in the bronchus and spleen in C57 mice receiving allogeneic tracheal transplantation when compared with mice with autologous transplantation, but the proportion of Treg cells was comparable between them. When compared with WT BalB/c mice, the proportion of Th2, Th17 and Treg cells reduced markedly and rejection reaction was attenuated in icos(-/-) mice receiving tracheal transplantation, although rejection reaction was still noted. icos knockout may delay the rejection reaction after tracheal transplantation, which might be ascribed to the imbalance among Th2, Th17 and Treg cells.American Journal of Translational Research 01/2014; 6(6):777-85. · 3.23 Impact Factor