Lymphoid neogenesis in chronic rejection: Evidence for a local humoral alloimmune response
- Olivier Thaunat*,†,
- Anne-Christine Field*,
- Jianping Dai‡,
- Liliane Louedec‡,
- Natacha Patey§,
- Marie-Françoise Bloch*,
- Chantal Mandet*,
- Marie-France Belair*,
- Patrick Bruneval*,
- Olivier Meilhac‡,
- Blanche Bellon*,
- Etienne Joly¶,
- Jean-Baptiste Michel‡,∥, and
- Antonino Nicoletti*,∥
- *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; ‡Institut National de la Santé et de la Recherche Médicale U698, Hôpital Xavier Bichat, 75870 Paris, France; §Department of Pathology, Hôpital Necker, 75270 Paris, France; and ¶Institut National de la Santé et de la Recherche Médicale U563, L'Institut Fédératif de Recherche Claude de Preval, 31300 Toulouse, France
-
Communicated by Jean Dausset, Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, Paris, France, August 29, 2005 (received for review June 10, 2005)
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.
Footnotes
-
↵ † To whom correspondence should be addressed at: Institut National de la Santé et de la Recherche Médicale U681, Institut des Cordeliers, 15 Rue de l'Ecole de Médecine, 75006 Paris, France. E-mail: olivier.thaunatpastu{at}free.fr.
-
↵ ∥ J.-B.M. and A.N. contributed equally to this work.
-
Abbreviations: HEV, high endothelial venule; PCNA, proliferating cell nuclear antigen.
- Copyright © 2005, The National Academy of Sciences
