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*
The Jackson Laboratory, Bar Harbor, ME 04609; and
Department of Medicine, University of Alberta, Edmonton, Canada
Numerous immunostimulatory protocols inhibit the development of T
cell-mediated autoimmune insulin-dependent diabetes mellitus (IDDM) in
the nonobese diabetic (NOD) mouse model. Many of these protocols,
including treatment with the nonspecific immunostimulatory agents CFA
or bacillus Calmette-Guérin (BCG) vaccine, have been reported to
mediate protection by skewing the pattern of cytokines produced by
pancreatic 
-cell autoreactive T cells from a Th1 (IFN-
) to a Th2
(IL-4 and IL-10) profile. However, most of these studies have
documented associations between such cytokine shifts and disease
protection rather than a cause/effect relationship. To partially
address this issue we produced NOD mice genetically deficient in
IFN-, IL-4, or IL-10. Elimination of any of these cytokines did not
significantly alter the rate of spontaneous IDDM development.
Additional experiments using these mice confirmed that CFA- or
BCG-elicited diabetes protection is associated with a decreased IFN-
to IL-4 mRNA ratio within T cell-infiltrated pancreatic islets, but
this is a secondary consequence rather than the cause of disease
resistance. Unexpectedly, we also found that the ability of BCG and, to
a lesser extent, CFA to inhibit IDDM development in standard NOD mice
is actually dependent upon the presence of the Th1 cytokine, IFN-.
Collectively, our studies demonstrate that while Th1 and Th2 cytokine
shifts may occur among -cell autoreactive T cells of NOD mice
protected from overt IDDM by various immunomodulatory therapies, it
cannot automatically be assumed that this is the cause of their disease
resistance.
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L. T. Mars, V. Laloux, K. Goude, S. Desbois, A. Saoudi, L. Van Kaer, H. Lassmann, A. Herbelin, A. Lehuen, and R. S. Liblau Cutting Edge: V{alpha}14-J{alpha}281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice J. Immunol., June 15, 2002; 168(12): 6007 - 6011. [Abstract] [Full Text] [PDF]
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G. Matarese, V. Sanna, R. I. Lechler, N. Sarvetnick, S. Fontana, S. Zappacosta, and A. La Cava Leptin Accelerates Autoimmune Diabetes in Female NOD Mice Diabetes, May 1, 2002; 51(5): 1356 - 1361. [Abstract] [Full Text] [PDF]
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A. Rabinovitch, W. L. Suarez-Pinzon, A.M. J. Shapiro, R. V. Rajotte, and R. Power Combination Therapy With Sirolimus and Interleukin-2 Prevents Spontaneous and Recurrent Autoimmune Diabetes in NOD Mice Diabetes, March 1, 2002; 51(3): 638 - 645. [Abstract] [Full Text] [PDF]
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A. C. Wiseman, B. A. Pietra, B. P. Kelly, G. R. Rayat, M. Rizeq, and R. G. Gill Donor IFN-{gamma} Receptors Are Critical for Acute CD4+ T Cell-Mediated Cardiac Allograft Rejection J. Immunol., November 1, 2001; 167(9): 5457 - 5463. [Abstract] [Full Text] [PDF]
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S. Trembleau, S. Gregori, G. Penna, I. Gorny, and L. Adorini IL-12 Administration Reveals Diabetogenic T Cells in Genetically Resistant I-E{alpha}-Transgenic Nonobese Diabetic Mice: Resistance to Autoimmune Diabetes Is Associated with Binding of E{alpha}-Derived Peptides to the I-Ag7 Molecule J. Immunol., October 1, 2001; 167(7): 4104 - 4114. [Abstract] [Full Text] [PDF]
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A. C. M. Johansson, A.-S. Hansson, K. S. Nandakumar, J. Backlund, and R. Holmdahl IL-10-Deficient B10.Q Mice Develop More Severe Collagen-Induced Arthritis, but Are Protected from Arthritis Induced with Anti-Type II Collagen Antibodies J. Immunol., September 15, 2001; 167(6): 3505 - 3512. [Abstract] [Full Text] [PDF]
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A. Bot, D. Smith, S. Bot, A. Hughes, T. Wolfe, L. Wang, C. Woods, and M. v. Herrath Plasmid Vaccination with Insulin B Chain Prevents Autoimmune Diabetes in Nonobese Diabetic Mice J. Immunol., September 1, 2001; 167(5): 2950 - 2955. [Abstract] [Full Text] [PDF]
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E. A. Johnson, P. Silveira, H. D. Chapman, E. H. Leiter, and D. V. Serreze Inhibition of Autoimmune Diabetes in Nonobese Diabetic Mice by Transgenic Restoration of H2-E MHC Class II Expression: Additive, But Unequal, Involvement of Multiple APC Subtypes J. Immunol., August 15, 2001; 167(4): 2404 - 2410. [Abstract] [Full Text] [PDF]
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