[Lymphoid neogenesis and lymphangiogenesis: two newcomers in the pathophysiology of chronic rejection].
Chronic rejection is one of the main causes of late allograft failure and no therapy is currently available to prevent efficiently its development. Improving the comprehension of the mechanisms involved in the pathophysiology of chronic rejection is a mandatory step to propose innovative therapies that would prolong grafts' survival. Using the rat aortic interposition model of chronic vascular rejection, we have demonstrated that the intragraft inflammatory infiltrate progressively organized itself into a functional ectopic lymphoid tissue (tertiary lymphoid organ) supporting the local synthesis of alloantibody. Thus, during chronic rejection the graft is at the same time the target and the site of elaboration of the humoral allo-immune response. This hypothesis has been confirmed in the clinical setting by the analysis of human grafts (kidneys, hearts and lungs) removed for terminal failure due to chronic rejection. This lymphoid neogenesis process, previously identified in other chronic inflammatory diseases, occurs with a strikingly high frequency in chronically rejected grafts, suggesting that an additional mechanism synergizes to initiate the development of tertiary lymphoid organs during chronic rejection. We propose that the defective lymphatic drainage of chronically rejected organs triggers lymphoid neogenesis and we discuss the complex crosstalk between lymphoid neogenesis and lymphangiogenesis that takes place during chronic rejection.
Attuil-Audenis
Valérie
V
U851, Inserm, université Claude-Bernard Lyon-1, and Department d'anatomopathologie, Hospital Edouard-Herriot HCL, 50, avenue Tony-Garnier, 69366 Lyon cedex 07, France.
Duthey
Aurélie
A
Patey
Natacha
N
Gautreau
Chantal
C
McGregor
Brigitte
B
Morelon
Emmanuel
E
Michel
Jean-Baptiste
JB
Nicoletti
Antonino
A
Thaunat
Olivier
O
D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology / Q000637:transplantation; D001705:Bioprosthesis / Q000009:adverse effects; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D002828:Choristoma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007431:Intraoperative Complications / Q000276:immunology / Q000503:physiopathology; D007518:Isoantibodies / Q000096:biosynthesis; D042583:Lymphangiogenesis / Q000502:physiology*; D042601:Lymphatic Vessels / Q000293:injuries / Q000503:physiopathology; D008221:Lymphoid Tissue / Q000503:physiopathology*; D051381:Rats; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology
D007518:Isoantibodies