1. Chronic rejection triggers the development of an aggressive intragraft immune response through recapitulation of lymphoid organogenesis.
- Author
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Thaunat O, Patey N, Caligiuri G, Gautreau C, Mamani-Matsuda M, Mekki Y, Dieu-Nosjean MC, Eberl G, Ecochard R, Michel JB, Graff-Dubois S, and Nicoletti A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, B-Lymphocytes immunology, B-Lymphocytes pathology, Cell Differentiation genetics, Cell Differentiation immunology, Cell Movement immunology, Chronic Disease, Female, Gene Expression Regulation immunology, Germinal Center immunology, Germinal Center pathology, Graft Rejection embryology, Graft Rejection pathology, Humans, Inflammation embryology, Inflammation immunology, Inflammation pathology, Kidney Cortex embryology, Kidney Cortex immunology, Kidney Cortex pathology, Kidney Transplantation pathology, Lymphoid Tissue pathology, Male, Middle Aged, Organogenesis genetics, Retrospective Studies, Tissue Culture Techniques, Graft Rejection immunology, Kidney Transplantation immunology, Lymphoid Tissue embryology, Lymphoid Tissue immunology, Organogenesis immunology
- Abstract
The unwarranted persistence of the immunoinflammatory process turns this critical component of the body's natural defenses into a destructive mechanism, which is involved in a wide range of diseases, including chronic rejection. Performing a comprehensive analysis of human kidney grafts explanted because of terminal chronic rejection, we observed that the inflammatory infiltrate becomes organized into an ectopic lymphoid tissue, which harbors the maturation of a local humoral immune response. Interestingly, intragraft humoral immune response appeared uncoupled from the systemic response because the repertoires of locally produced and circulating alloantibodies only minimally overlapped. The organization of the immune effectors within adult human inflamed tissues recapitulates the biological program recently identified in murine embryos during the ontogeny of secondary lymphoid organs. When this recapitulation was incomplete, intragraft B cell maturation was impeded, limiting the aggressiveness of the local humoral response. Identification of the molecular checkpoints critical for completion of the lymphoid neogenesis program should help develop innovative therapeutic strategies to fight chronic inflammation.
- Published
- 2010
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