title: Lymphoid neogenesis in chronic rejection: evidence for a local humoral alloimmune response.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U681, Institut Biomédical des Cordeliers, Université Pierre et Marie Curie, Paris VI 75006 Paris, France. olivier.thaunatpastu@free.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Thaunat
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Field
authors.forename: Jianping
authors.initials: J
authors.lastname: Dai
authors.forename: Liliane
authors.initials: L
authors.lastname: Louedec
authors.forename: Natacha
authors.initials: N
authors.lastname: Patey
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Bloch
authors.forename: Chantal
authors.initials: C
authors.lastname: Mandet
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Belair
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Olivier
authors.initials: O
authors.lastname: Meilhac
authors.forename: Blanche
authors.initials: B
authors.lastname: Bellon
authors.forename: Etienne
authors.initials: E
authors.lastname: Joly
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Antonino
authors.initials: A
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D001011:Aorta / Q000276:immunology / Q000637:transplantation* / Q000648:ultrastructure; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000276:immunology* / Q000648:ultrastructure; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I