Lymphoid neogenesis in chronic rejection: evidence for a local humoral alloimmune response.
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.
Thaunat
Olivier
O
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
Field
Anne-Christine
AC
Dai
Jianping
J
Louedec
Liliane
L
Patey
Natacha
N
Bloch
Marie-Françoise
MF
Mandet
Chantal
C
Belair
Marie-France
MF
Bruneval
Patrick
P
Meilhac
Olivier
O
Bellon
Blanche
B
Joly
Etienne
E
Michel
Jean-Baptiste
JB
Nicoletti
Antonino
A
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
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I