Autoimmune diabetes can be induced in transgenic major histocompatibility complex class II-deficient mice.
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease marked by hyperglycemia and mononuclear cell infiltration of insulin-producing beta islet cells. Predisposition to IDDM in humans has been linked to the class II major histocompatibility complex (MHC), and islet cells often become aberrantly class II positive during the course of the disease. We have used two recently described transgenic lines to investigate the role of class II molecules and CD4+ T cells in the onset of autoimmune insulitis. Mice that are class II deficient secondary to a targeted disruption of the A beta b gene were bred to mice carrying a transgene for the lymphocytic choriomenigitis virus (LCMV) glycoprotein (GP) targeted to the endocrine pancreas. Our results indicate that class II-deficient animals with and without the GP transgene produce a normal cytotoxic T lymphocyte response to whole LCMV. After infection with LCMV, GP-transgenic class II-deficient animals develop hyperglycemia as rapidly as their class II-positive littermates. Histologic examination of tissue sections from GP-transgenic class II-deficient animals reveals lymphocytic infiltrates of the pancreatic islets that are distinguishable from those of their class II-positive littermates only by the absence of infiltrating CD4+ T cells. These results suggest that in this model of autoimmune diabetes, CD4+ T cells and MHC class II molecules are not required for the development of disease.
Laufer
T M
TM
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts.
von Herrath
M G
MG
Grusby
M J
MJ
Oldstone
M B
MB
Glimcher
L H
LH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II