A viral epitope that mimics a self antigen can accelerate but not initiate autoimmune diabetes.
We document here that infection of prediabetic mice with a virus expressing an H-2Kb-restricted mimic ligand to a self epitope present on beta cells accelerates the development of autoimmune diabetes. Immunization with the mimic ligand expanded autoreactive T cell populations, which was followed by their trafficking to the islets, as visualized in situ by tetramer staining. In contrast, the mimic ligand did not generate sufficient autoreactive T cells in naive mice to initiate disease. Diabetes acceleration did not occur in H-2Kb-deficient mice or in mice tolerized to the mimic ligand. Thus, arenavirus-expressed mimics of self antigens accelerate a previously established autoimmune process. Sequential heterologous viral infections might therefore act in concert to precipitate clinical autoimmune disease, even if single exposure to a viral mimic does not always cause sufficient tissue destruction.
Christen
Urs
U
Immune Regulation Lab, Department of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Edelmann
Kurt H
KH
McGavern
Dorian B
DB
Wolfe
Tom
T
Coon
Bryan
B
Teague
Meghann K
MK
Miller
Stephen D
SD
Oldstone
Michael B A
MB
von Herrath
Matthias G
MG
D000818:Animals; D001324:Autoantigens / Q000737:chemistry*; D001402:B-Lymphocytes / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes / Q000737:chemistry; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors; D019076:Transgenes
D001324:Autoantigens; D001786:Blood Glucose; D016207:Cytokines; D000939:Epitopes; D008024:Ligands