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-mediated apoptosis of insulin-producing beta cells. We have previously shown that Th2 T cells bearing the same T cell receptor (TCR) as the diabetogenic Th1 T cells invade islets in neonatal nonobese diabetic (NOD) mice but fail to cause disease. Moreover, when mixed in excess and cotransferred with Th1 T cells, Th2 T cells could not protect NOD neonates from Th1-mediated diabetes. We have now found, to our great surprise, the same Th2 T cells that produced a harmless insulitis in neonatal NOD mice produced intense and generalized pancreatitis and insulitis associated with islet cell necrosis, abscess formation, and subsequent diabetes when transferred into immunocompromised NOD.scid mice. These lesions resembled allergic inflamation and contained a large eosinophilic infiltrate. Moreover, the Th2-mediated destruction of islet cells was mediated by local interleukin-10 (IL-10) production but not by IL-4. These findings indicate that under certain conditions Th2 T cells may not produce a benign or protective insulitis but rather acute pathology and disease. Additionally, these results lead us to question the feasibility of Th2-based therapy in type I diabetes, especially in immunosuppressed recipients of islet cell transplants.
Pakala
S V
SV
Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kurrer
M O
MO
Katz
J D
JD
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D016753:Interleukin-10 / Q000502:physiology; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000209:etiology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology*
D016753:Interleukin-10