Autoimmune diabetes is caused by the CD4+, T helper 1 (Th1) cell-mediated apoptosis of insulin-producing β 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.
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21 July 1997
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July 21 1997
T Helper 2 (Th2) T Cells Induce Acute Pancreatitis and Diabetes in Immune-compromised Nonobese Diabetic (NOD) Mice
Syamasundar V. Pakala,
Syamasundar V. Pakala
From the Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
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Michael O. Kurrer,
Michael O. Kurrer
From the Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
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Jonathan D. Katz
Jonathan D. Katz
From the Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
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Syamasundar V. Pakala
From the Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
Michael O. Kurrer
From the Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
Jonathan D. Katz
From the Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110
Address correspondence to J.D. Katz, Department of Pathology and Center for Immunology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid, St. Louis, Missouri 63110. Phone: 314-747-1221; Fax: 314-747-0728; E-mail: [email protected]
1 Abbreviations used in this paper: AEC, aminoethylcarbazole; DAB, diaminobenzidine; IDDM, insulin-dependent diabetes mellitus; PNA, peripheral node addressin.
Received:
April 25 1997
Revision Received:
May 09 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (2): 299–306.
Article history
Received:
April 25 1997
Revision Received:
May 09 1997
Citation
Syamasundar V. Pakala, Michael O. Kurrer, Jonathan D. Katz; T Helper 2 (Th2) T Cells Induce Acute Pancreatitis and Diabetes in Immune-compromised Nonobese Diabetic (NOD) Mice. J Exp Med 21 July 1997; 186 (2): 299–306. doi: https://doi.org/10.1084/jem.186.2.299
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