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 be ta cell-specific Th2 cells in regulating insulin-dependent diabetes (IDDM). Whether a homogeneous population of Th2 cells having a defined beta cell A g 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 s pecific for glutamic acid decarboxylase 65 (GAD65), a known beta cell autoa ntigen, from young unimmunized nonobese diabetic (NOD) mice. Adoptive trans fer of a GAD65-specific Th2 cell clone (characterized by the secretion of I L-4, IL-5, and IL-10, but not IFN-gamma or TGF-beta) into 2- or 12-wk-old N OD 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 autoanti gens 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. T hese results provide direct evidence that beta cell-specific Th2 cells can indeed prevent and suppress autoimmune diabetes in NOD mice.