Autoimmune insulitis and diabetes in the absence of antigen-specific contact between T cells and islet beta-cells.
Autoimmune diabetes develops following recognition of organ-specific antigens by T cells. The disease begins with peri-islet infiltration by mononuclear cells, proceeds with insulitis and becomes manifest with destruction of insulin-producing islet beta-cells. T cells are necessary to induce insulitis and diabetes, but it is not clear by what mechanisms they can do so, i. e. whether the T cells need to make antigen-specific contact with the beta-cell or whether other interactions are sufficient to induce beta-cell death. In the present study we have constructed chimeric mice in which the bone marrow-derived antigen-presenting cells, but not the islet beta-cells, are capable of presenting antigen to monospecific T cells. We show that both insulitis as well as beta-cell destruction can proceed in the absence of islet beta-cell surface antigen recognition by T cells. Our results support the notion that diabetes can be caused by distinct effector mechanisms.
Sarukhan
A
A
Institut Necker, INSERM U373, Paris, France.
Lechner
O
O
von Boehmer
H
H
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016654:Genes, RAG-1 / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D020799:Pancrelipase / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D019076:Transgenes / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020799:Pancrelipase