A glutamic acid decarboxylase 65-specific Th2 cell clone immunoregulates autoimmune diabetes in nonobese diabetic mice.
Several studies have provided indirect evidence in support of a role for beta cell-specific Th2 cells in regulating insulin-dependent diabetes (IDDM). Whether a homogeneous population of Th2 cells having a defined beta cell Ag specificity can prevent or suppress autoimmune diabetes is still unclear. In fact, recent studies have demonstrated that beta cell-specific Th2 cell clones can induce IDDM. In this study we have established Th cell clones specific for glutamic acid decarboxylase 65 (GAD65), a known beta cell autoantigen, from young unimmunized nonobese diabetic (NOD) mice. Adoptive transfer of a GAD65-specific Th2 cell clone (characterized by the secretion of IL-4, IL-5, and IL-10, but not IFN-gamma or TGF-beta) into 2- or 12-wk-old NOD female recipients prevented the progression of insulitis and subsequent development of overt IDDM. This prevention was marked by the establishment of a Th2-like cytokine profile in response to a panel of beta cell autoantigens in cultures established from the spleen and pancreatic lymph nodes of recipient mice. The immunoregulatory function of a given Th cell clone was dependent on the relative levels of IFN-gamma vs IL-4 and IL-10 secreted. These results provide direct evidence that beta cell-specific Th2 cells can indeed prevent and suppress autoimmune diabetes in NOD mice.
Tisch
R
R
Department of Microbiology and Immunology, Mary Ellen Jones Building, Room 804, Campus Box 7290, University of North Carolina, Chapel Hill, NC 27599-7290, USA. mtisch@med.unc.edu
Wang
B
B
Atkinson
M A
MA
Serreze
D V
DV
Friedline
R
R
D019264:Adoptive Transfer; D017668:Age of Onset; D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D007527:Isoenzymes / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology; D018418:Th2 Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007527:Isoenzymes; D015847:Interleukin-4; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2