A glutamic acid decarboxylase 65-specific Th2 cell clone immunoregulates autoimmune diabetes in nonobese diabetic mice.
Age-of-Onset, Animal, Cell-Culture, Cell-Movement, Clone-Cells, Cytokines, Diabetes-Mellitus, Epitopes-T-Lymphocyte, Female, Glutamate-Decarboxylase, Interleukin-4, Islets-of-Langerhans, Isoenzymes, Mice, Mice-Inbred-NOD, Mice-SCID, Spleen, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocyte-Subsets, T-Lymphocytes-Helper-Inducer, Th2-Cells
J Immunol 2001 Jun; 166(11):6925-36.
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; Wang, B; Atkinson, M A.; Serreze, D V.; and Friedline, R, " A glutamic acid decarboxylase 65-specific Th2 cell clone immunoregulates autoimmune diabetes in nonobese diabetic mice." (2001). Faculty Research 2000 - 2009. 227.