Prevention of type I diabetes transfer by glutamic acid decarboxylase 65 peptide 206-220-specific T cells.
Glutamic acid decarboxylase (GAD) 65 is one of the major pancreatic antigens targeted by self-reactive T cells in type I diabetes mellitus. T cells specific for GAD65 are among the first to enter inflamed islets and may be important for the initiation of autoimmune diabetes. However, we previously reported that nonobese diabetic (NOD) mice transgenic for a T cell antigen receptor (TCR) specific for one of the immunodominant epitopes of GAD65, peptide 286-300 (G286), are protected from insulitis and diabetes. To examine whether other GAD65-reactive T cells share this phenotype, we have generated TCR transgenic NOD mice for a second immunodominant epitope of GAD65, peptide 206-220 (G206). As in G286 mice, G206 mice do not develop islet inflammation or diabetes. When adoptively transferred along with diabetogenic T cells, activated G206 T cells significantly delayed the onset of diabetes in NOD.scid recipients. Both G206 and G286 T cells produce immunoregulatory cytokines IFN-gamma and IL-10 at low levels when activated by cognate antigens. These data suggest that GAD65-specific T cells may play a protective role in diabetes pathogenesis by regulating pathogenic T cell responses. A better understanding of the functions of autoreactive T cells in type I diabetes will be necessary for choosing desirable targets for immunotherapy.
Kim
Seon-Kyeong
SK
Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
Tarbell
Kristin V
KV
Sanna
Maija
M
Vadeboncoeur
Mary
M
Warganich
Tibor
T
Lee
Mark
M
Davis
Mark
M
McDevitt
Hugh O
HO
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000032:analysis; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000378:metabolism; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D007371:Interferon-gamma; D005968:Glutamate Decarboxylase; D005947:Glucose