Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response.
We investigated the potential association between viruses and insulin-dependent (type 1) diabetes (IDDM) by developing a transgenic mouse model. By inserting into these mice a unique viral protein that was then expressed as a self-antigen in the pancreatic islets of Langerhans, we could study the effect on that expressed antigen alone, or in concert with an induced antiviral (i.e., autoimmune) response manifested later in life in causing IDDM. Our results indicate that a viral gene introduced as early as an animal's egg stage, incorporated into the germline, and expressed in islet cells does not produce tolerance when the host is exposed to the same virus later in life. We observed that the induced anti-self (viral) CTL response leads to selective and progressive damage of beta cells, resulting in IDDM.
Oldstone
M B
MB
Department of Neuropharmacology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Nerenberg
M
M
Southern
P
P
Price
J
J
Lewicki
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics / Q000382:microbiology*; D001786:Blood Glucose / Q000378:metabolism; D016827:CD8 Antigens; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D005814:Genes, Viral; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D001786:Blood Glucose; D016827:CD8 Antigens; D007328:Insulin; D014764:Viral Proteins