1. Bone marrow-derived immature dendritic cells prime in vivo alloreactive T cells for interleukin-4-dependent rejection of major histocompatibility complex class II antigen-disparate cardiac allograft
- Author
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Michel Goldman, Michel Y Braun, Sofia Buonocore, and Véronique Flamand
- Subjects
CD4-Positive T-Lymphocytes ,Graft Rejection ,Bone Marrow Cells -- immunology ,Gene Expression ,Cell Communication ,Cell Communication -- immunology ,Dendritic Cells -- immunology ,Mice ,Cell Differentiation -- immunology ,Cells, Cultured ,biology ,Graft Survival ,Dendritic Cells -- cytology ,Cell Differentiation ,Sciences bio-médicales et agricoles ,Granulocyte-Macrophage Colony-Stimulating Factor -- pharmacology ,Transplant rejection ,Interleukin-5 -- genetics ,Cell Differentiation -- drug effects ,Dendritic Cells -- drug effects ,Graft Rejection -- immunology ,Interleukin-4 -- genetics ,medicine.drug ,Gene Expression -- immunology ,Interleukin 2 ,Bone Marrow Cells ,Bone Marrow Cells -- cytology ,Major histocompatibility complex ,Heart Transplantation -- immunology ,Immunophenotyping ,Interferon-gamma ,Antigen ,medicine ,Animals ,Transplantation, Homologous ,Interferon-gamma -- genetics ,Interleukin 4 ,Transplantation ,Histocompatibility Antigens Class II -- immunology ,CD4-Positive T-Lymphocytes -- immunology ,Histocompatibility Antigens Class II ,Granulocyte-Macrophage Colony-Stimulating Factor ,Dendritic cell ,Dendritic Cells ,medicine.disease ,Graft Survival -- immunology ,Mice, Inbred C57BL ,Interleukin-4 -- immunology ,Immunology ,Chronic Disease ,biology.protein ,Heart Transplantation ,CD4-Positive T-Lymphocytes -- cytology ,Interleukin-4 ,Interleukin-5 ,CD8 - Abstract
BACKGROUND: Dendritic cells (DC) at the immature state express low levels of major histocompatibility complex and costimulatory molecules and are poor stimulators of primary T-cell response in vitro. Injection of immature bone marrow-derived DC, however, was shown to prime in vivo alloreactive CD4 T lymphocytes toward type 2 cytokine-producing cells in the absence of CD8 T-cell activation. METHODS: We undertook the present study to determine whether Th2-immunization by immature DC could lead to allograft rejection. We first analyzed, in the major histocompatibility complex class II antigen-disparate B6-anti-bm12 combination, the capacity of immature DC to regulate the activity of alloreactive CD4 T cells. We then determined, in this model of weak antigenicity, whether injection of bm12 DC in B6 recipients before transplantation could modify the survival of vascularized bm12 cardiac allografts. RESULTS: We confirmed that in vitro immature DC are poor stimulators of T-cell alloresponse. However, when given in vivo, immature bm12 DC primed anti-bm12 T cells for the production of interleukin (IL)-4. Moreover, they induced the acute rejection of bm12 cardiac allograft. The process of rejection was dependent on IL-4 because immunization of IL-4-deficient mice did not trigger rejection. CONCLUSIONS: Allogeneic immature DC generated with granulocyte-macrophage colony-stimulating factor are potent stimulators of primary alloreactive response in vivo and prime for transplant rejection. Our results indicate that strategies based on immature DC for the induction of transplantation tolerance should be considered with caution., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published
- Published
- 2003