Lymphoid Neogenesis in Chronic Rejection: Evidence for a Local Humoral Alloimmune Response

• Published in: Proceedings of the National Academy of Sciences - PNAS 2005-10, Vol.102 (41), p.14723-14728
• Main Authors: Olivier Thaunat, Anne-Christine Field, Jianping Dai, Liliane Louedec, Natacha Patey, Marie-Françoise Bloch, Chantal Mandet, Belair, Marie-France, Bruneval, Patrick, Olivier Meilhac, Bellon, Blanche, Joly, Etienne, Michel, Jean-Baptiste, Antonino Nicoletti
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - immunology; Antibody Formation - immunology; Aorta - immunology; Aorta - transplantation; Aorta - ultrastructure; Apoptosis - immunology; B lymphocytes; B-Lymphocytes - immunology; Biological Sciences; Cell Proliferation; Chronic illnesses; Endothelial cells; Endothelial Cells - immunology; Endothelial Cells - ultrastructure; Flow Cytometry; Graft rejection; Graft Rejection - immunology; Histocompatibility Antigens Class I - immunology; Immune system; Immunohistochemistry; Lymphocyte receptors; Lymphocytes; Lymphoid tissue; Male; Microscopy, Electron, Transmission; Rats; Rats, Inbred Lew; T lymphocytes; Tissue grafting; Transplantation; Vascular grafting
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0507223102

Recent advances indicate that, in various chronic inflammatory disorders, the activation of the immune system is triggered locally rather than in lymphoid organs. In this study, we have evaluated whether the humoral alloimmune response involved in chronic rejection is elicited within the graft. We used the rat aortic interposition model and microdissected the adventitia of the graft. Over time, the T cell infiltrate shifted toward a B helper phenotype. B lymphocyte clusters were detected and were the site of intense proliferation and apoptosis. Simultaneously, adventitial vascular endothelium acquired a high endothelial venule phenotype. Similar features were evidenced in the interstitium of chronically allografts (hearts and kidneys). Strikingly, ganocultured graft interstitial tissue was found to be the site of production of antibodies directed against donor MHC-I molecules. These findings, therefore, document the appearance of germinal centers in chronically rejected tissues. This lymphoid neogenesis implies that the graft is not only the target of the alloimmune response but also a site where this response actually develops, so as to optimize the communication between the targeted tissue and the immune effectors.