Tolerance induction to self antigens by peripheral dendritic cells.
It has been suggested, but not formally demonstrated, that peripheral dendritic cells (DC) alone are capable of tolerance induction by clonal deletion and/or anergy. To resolve such an issue, it is important to develop in vivo systems where DC are the only cells capable of presenting antigen and where a T cell population with a known antigen specificity can be followed. Here we use a transgenic murine model, which expresses the influenza virus hemagglutinin (HA) on B cells and on CD8alpha(+) and CD8alpha(-) DC but not on macrophages. If these mice are on a RAG(-/-) background, one has a model in which only DC present the HA antigen. In these mice, HA-specific T cells are deleted very efficiently in the thymus and those remaining in the periphery cannot respond to further antigenic stimulation in vitro and cannot eliminate antigen in vivo. By performing adoptive transfers, we show for the first time that self-antigen presentation exclusively by peripheral DC results in very efficient clonal deletion of the majority of antigen-specific T cells with the remaining ones in an anergic state. This model will permit us to further address the mechanisms by which DC tolerize or prime T cells and to investigate whether anergy induction by DC is similar to anergy induction by B cells.
INSERM U345, Institut Necker, Paris, France.
Florence
F
Lambolez
Karin
K
Jooss
Florence
F
Vasseur
Adelaida
A
Sarukhan
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation; D039521:CD11c Antigen / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D017635:Clonal Anergy; D017637:Clonal Deletion; D003713:Dendritic Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018398:Homeodomain Proteins / Q000502:physiology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D011828:Radiation Chimera; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D013950:Thymus Gland / Q000276:immunology
D000956:Antigens, Viral; D001324:Autoantigens; D039521:CD11c Antigen; D016827:CD8 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C064658:RAG-1 protein