Background: Anti-MHC class I administration into lungs results in cellular infiltration, epithelial damage, immune responses to lung associated self-antigens(SAgs), KΑ1 tubulin (KΑ1T) and Collagen V (ColV), leading to obliterative airway disease (OAD), correlate of chronic rejection following human lung transplantation. The goal of this study was to define the role of T cells and their subsets infiltrated into the lungs following administration of anti-MHC in the pathogenesis of OAD.
Materials and Methods: Antibodies (Abs) to MHC class I was administered intrabronchially into C57BL/6 animals. Infiltrating CD8+ and CD4+ T cell subsets were purified from the lung and passively administered intrabronchially into naÏve animals. Lungs were analyzed by histopathology and immunohistochemistry. Frequency of cells secreting IL-17, IFN-Γ or IL-10 to ColV and KΑ1T were enumerated by ELISpot. Myeloperoxidase and Abs to SAgs were determined by ELISA. Cytokine and growth factor expression was determined by qRT-PCR.
Results: Intrabronchial administration of anti-MHC resulted in cellular infiltration into lungs by neutrophils, macrophages and CD8+ T cells by day 15; and B cells and CD4+ T cells by day 30 prior to development of OAD. Passive transfer of CD8 transfer induced cellular infiltration of neutrophils and macrophages suggesting early injury response. In contrast, passive transfer of CD4+ T cells induced B cell infiltration leading to immune responses to lung associated SAgs and fibrosis. There was increase in IL-17 (p<0.05) secreting cells to SAgs along with serum Abs to SAgs (p<0.05) with CD4 transfer over CD8. The expression of IL-6, TGF-Β and pro-fibrotic growth factors were also increased with CD4 over CD8 transfer.
Conclusion: Ligation of MHC molecules in the lungs by its specific Abs induced infiltration of neutrophils, macrophages and CD8 T cells leading to injury to the epithelium and exposure of SAgs or determinants. SAgs are presented by the infiltrating CD4+ T cells and B cells leading to immune responses to SAgs culminating in OAD. We present a novel role of allo-antibodies in the induction of inflammatory cellular infiltration leading to immune responses not only to allo-antigens but also to tissue restricted SAgs.
To cite this abstract in AMA style:Tiriveedhi V, Takenaka M, Sarma N, Gelman A, Mohanakumar T. Unique Role of Antibodies to MHC Class I in the Induction of Inflammatory Cellular Infiltration: Selective Role for CD4 and CD8 Cells in Development of Autoimmunity and Obliterative Airway Disease [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/unique-role-of-antibodies-to-mhc-class-i-in-the-induction-of-inflammatory-cellular-infiltration-selective-role-for-cd4-and-cd8-cells-in-development-of-autoimmunity-and-obliterative-airway-disease/. Accessed May 15, 2021.
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