The T cell response to glutamic acid decarboxylase 65 in T cell receptor transgenic NOD mice.
Using BW 5147 T cell hybridomas isolated by fusion with spleen and lymph node cells from NOD female mice, two T cell receptor transgenic NOD mouse lines were produced. Both TCR transgenics respond to their cognate peptide/MHC (GAD65 206-220 and 286-300) and produce IL-2, IFN-gamma, and small amounts of IL-10. Unexpectedly, the transgenic mice do not develop diabetes and have no insulitis. Analysis with a GAD65 286-300/I-A(g7) tetramer reveals that transgenic T cells are negatively selected in the thymus and further negatively selected in the periphery. When crossed to the C(alpha)(-/-) NOD line, CD4 T cells were reduced by 90% in the thymus and periphery. Further, the tetramer positive GAD65 286-300 specific T cells were capable of delaying the onset of diabetes in a standard transfer system. Thus, GAD65 specific TCR transgenic T cells (1) must express a second a chain to survive negative selection, (2) produce IL-2 and IFN-gamma, and (3) have a mildly protective effect on transfer of diabetes with diabetogenic spleen cells.
McDevitt
Hugh
H
Departments of Microbiology and Immunology, and Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. hughmcd@stanford.edu
D000818:Animals; D005260:Female; D005968:Glutamate Decarboxylase / Q000502:physiology*; D007527:Isoenzymes / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D007527:Isoenzymes; D011948:Receptors, Antigen, T-Cell; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2