Prolongation of heart allograft survival by immature dendritic cells generated from recipient type bone marrow progenitors.
Recent studies suggest that particular dendritic cells (DC) subpopulations may be tolerogenic. To test the capacity of different DC subpopulations to modulate allograft rejection, we generated two distinct populations of rat bone marrow-derived DCs (BMDC) with low doses of GM-CSF and IL-4. The non-adherent population (nBMDC), which are the 'classical' DCs was able to stimulate naive allogeneic T cells and could be induced to completely mature using various stimuli. In contrast, the adherent population (aBMDC), which displayed an immature phenotype, was unable to stimulate T cells and was more resistant to maturation. We found that syngeneic aBMDCs, injected one day before transplantation, induced significant prolongation of heart allograft survival and decreased anti-donor humoral and cellular responses. Similarly, syngeneic aBMDCs inhibited T-cell responses to KLH in the spleen but not in lymph node in a KLH immunization model without graft. This effect was not antigen specific and could be reversed using an inhibitor of inducible nitric oxide synthase. This compartmentalized inhibition could be in part explained by the fact that the majority of syngeneic adherent cells administered intravenously were found in the spleen with some of them reaching the T-cell areas. These data suggest that syngeneic aBMDCs can modulate immune responses.
Pêche
Hélène
H
Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 437 and Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, Cedex 1 France. hpeche@mail.jci.tju.edu
Trinité
Benjamin
B
Martinet
Bernard
B
Cuturi
Maria Cristina
MC
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D003713:Dendritic Cells / Q000502:physiology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000502:physiology*; D016027:Heart Transplantation; D006433:Hemocyanins / Q000276:immunology; D051379:Mice; D051381:Rats; D013154:Spleen / Q000502:physiology; D013234:Stem Cells / Q000276:immunology / Q000502:physiology*
D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin