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.
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.
Buonocore
Sofia
S
Laboratory of Experimental Immunology, Universite Libre de Bruxelles, route de Lennik 808, 1070 Brussels, Belgium.
Flamand
Véronique
V
Goldman
Michel
M
Braun
Michel Y
MY
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002908:Chronic Disease; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016027:Heart Transplantation / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D014184:Transplantation, Homologous
D000949:Histocompatibility Antigens Class II; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor