T-lymphocyte lines specific for glutamic acid decarboxylase (GAD) the 64K beta-cell antigen of IDDM.
Insulin-dependent diabetes mellitus (IDDM) is viewed as a thymus-dependent autoimmune disease, although the specific beta-cell autoantigen or autoantigens remain unknown. The recent identification of the beta-cell 64K antigen as the enzyme glutamic acid decarboxylase (GAD) permits investigation of GAD as a candidate for the autoantigen associated with beta-cell destruction, mediated by T-lymphocytes, in susceptible individuals. In this study, we describe the isolation of GAD-specific T-lymphocyte lines from BB rats, an animal model of IDDM. GAD (Escherichia coli) was inoculated into the footpads of diabetes-resistant BB rats, and after 10 days, a popliteal lymph node cell culture suspension was prepared. GAD-specific T lymphocytes were obtained by culture with interleukin 2 and repeated stimulation with GAD in the presence of BB rat thymic antigen-presenting cells. Four stable, CD4+, MHC (RT1u)-restricted T-lymphocyte lines were isolated. They proliferate selectively in the presence of GAD and secrete interleukin 2 and interferon-gamma. T-lymphocyte lines such as these could be important in the definition of pathogenetic epitopes associated with GAD.
Diaz
J L
JL
Department of Cell Biology, Glaxo Research Institute, Research Triangle Park, NC 27709.
Ways
J
J
Hammonds
P
P
D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001324:Autoantigens / Q000032:analysis*; D003429:Cross Reactions; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D004926:Escherichia coli / Q000201:enzymology; D005968:Glutamate Decarboxylase / Q000032:analysis / Q000276:immunology*; D007515:Islets of Langerhans / Q000201:enzymology / Q000276:immunology*; D008213:Lymphocyte Activation; D008970:Molecular Weight; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D005968:Glutamate Decarboxylase