T-HELPER-2 (TH2) T-CELLS INDUCE ACUTE-PANCREATITIS AND DIABETES IN IMMUNE-COMPROMISED NONOBESE DIABETIC (NOD) MICE

Autoimmune diabetes is caused by the CD4(+), T helper 1 (Th1) cell-med iated apoptosis of insulin-producing beta cells. We have previously sh own that Th2 T cells bearing the same T cell receptor (TCR) as the dia betogenic Th1 T cells invade islets in neonatal nonobese diabetic (NOD ) mice but fail to cause disease. Moreover, when mixed in excess and c otransferred with Th1 T cells, Th2 T cells could not protect NOD neona tes from Th1-mediated diabetes. We have now found, to our great surpri se, the same Th2 T cells that produced a harmless insulitis in neonata l NOD mice produced intense and generalized pancreatitis and insulitis associated with islet cell necrosis, abscess formation, and subsequen t diabetes when transferred into immunocompromised NOD.scid mice. Thes e lesions resembled allergic inflamation and contained a large eosinop hilic infiltrate. Moreover, the Th2-mediated destruction of islet cell s was mediated by local interleukin-10 (IL-10) production but not by I L-4. These findings indicate that under certain conditions Th2 T cells may not produce a benign or protective insulitis but rather acute pat hology and disease. Additionally, these results lead us to question th e feasibility of TH2-based therapy in type I diabetes, especially in i mmunosuppressed recipients of islet cell transplants.