The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Serreze, D. V.
Right arrow Articles by Rabinovitch, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Serreze, D. V.
Right arrow Articles by Rabinovitch, A.
The Journal of Immunology, 2001, 166: 1352-1359.
Copyright © 2001 by The American Association of Immunologists

Th1 to Th2 Cytokine Shifts in Nonobese Diabetic Mice: Sometimes an Outcome, Rather Than the Cause, of Diabetes Resistance Elicited by Immunostimulation1

David V. Serreze2,*, Harold D. Chapman*, Cristina M. Post*, Ellis A. Johnson*, Wilma L. Suarez-Pinzon{dagger} and Alex Rabinovitch{dagger}

* The Jackson Laboratory, Bar Harbor, ME 04609; and {dagger} 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 {beta}-cell autoreactive T cells from a Th1 (IFN-{gamma}) 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-{gamma}, 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-{gamma} 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-{gamma}. Collectively, our studies demonstrate that while Th1 and Th2 cytokine shifts may occur among {beta}-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.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
J. H. Esensten, M. R. Lee, L. H. Glimcher, and J. A. Bluestone
T-bet-Deficient NOD Mice Are Protected from Diabetes Due to Defects in Both T Cell and Innate Immune System Function
J. Immunol., July 1, 2009; 183(1): 75 - 82.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Solvason, Y.-P. Lou, W. Peters, E. Evans, J. Martinez, U. Ramirez, A. Ocampo, R. Yun, S. Ahmad, E. Liu, et al.
Improved Efficacy of a Tolerizing DNA Vaccine for Reversal of Hyperglycemia through Enhancement of Gene Expression and Localization to Intracellular Sites
J. Immunol., December 15, 2008; 181(12): 8298 - 8307.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Ueno, J. Wang, L. Cheng, J. S. Im, Y. Shi, S. A. Porcelli, and Y. Yang
Enhanced Early Expansion and Maturation of Semi-Invariant NK T Cells Inhibited Autoimmune Pathogenesis in Congenic Nonobese Diabetic Mice
J. Immunol., November 15, 2008; 181(10): 6789 - 6796.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
Y. Mori, T. Kato, T. Kodaka, E. M. Kanagawa, S. Hori, and O. Kanagawa
Protection of IFN-{gamma} signaling-deficient NOD mice from diabetes by cyclophosphamide
Int. Immunol., September 1, 2008; 20(9): 1231 - 1237.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Hussain and T. L. Delovitch
Intravenous Transfusion of BCR-Activated B Cells Protects NOD Mice from Type 1 Diabetes in an IL-10-Dependent Manner
J. Immunol., December 1, 2007; 179(11): 7225 - 7232.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. L.-T. Chang, S.-L. Chang, Y.-M. Lee, Y.-M. Chiang, D.-Y. Chuang, H.-K. Kuo, and W.-C. Yang
Cytopiloyne, a Polyacetylenic Glucoside, Prevents Type 1 Diabetes in Nonobese Diabetic Mice
J. Immunol., June 1, 2007; 178(11): 6984 - 6993.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
A. Ueno, S. Cho, L. Cheng, J. Wang, S. Hou, H. Nakano, P. Santamaria, and Y. Yang
Transient Upregulation of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Human Chorionic Gonadotropin Downregulates Autoimmune Diabetes
Diabetes, June 1, 2007; 56(6): 1686 - 1693.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
Y. Shibata, R. A. Henriksen, I. Honda, R. M. Nakamura, and Q. N. Myrvik
Splenic PGE2-releasing macrophages regulate Th1 and Th2 immune responses in mice treated with heat-killed BCG
J. Leukoc. Biol., December 1, 2005; 78(6): 1281 - 1290.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Bour-Jordan, H. L. Thompson, and J. A. Bluestone
Distinct Effector Mechanisms in the Development of Autoimmune Neuropathy versus Diabetes in Nonobese Diabetic Mice
J. Immunol., November 1, 2005; 175(9): 5649 - 5655.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. S. Smith, T. Patterson, and M. E. Pauza
Transgenic Ly-49A Inhibits Antigen-Driven T Cell Activation and Delays Diabetes
J. Immunol., April 1, 2005; 174(7): 3897 - 3905.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Novak, L. Beaudoin, T. Griseri, and A. Lehuen
Inhibition of T Cell Differentiation into Effectors by NKT Cells Requires Cell Contacts
J. Immunol., February 15, 2005; 174(4): 1954 - 1961.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
D. V. Serreze, C. Wasserfall, E. W. Ottendorfer, M. Stalvey, M. A. Pierce, C. Gauntt, B. O'Donnell, J. B. Flanagan, M. Campbell-Thompson, T. M. Ellis, et al.
Diabetes Acceleration or Prevention by a Coxsackievirus B4 Infection: Critical Requirements for both Interleukin-4 and Gamma Interferon
J. Virol., January 15, 2005; 79(2): 1045 - 1052.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. K. Gregg, J. J. Bell, H.-H. Lee, R. Jain, S. J. Schoenleber, R. Divekar, and H. Zaghouani
IL-10 Diminishes CTLA-4 Expression on Islet-Resident T Cells and Sustains Their Activation Rather Than Tolerance
J. Immunol., January 15, 2005; 174(2): 662 - 670.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. K. Gregg, R. Jain, S. J. Schoenleber, R. Divekar, J. J. Bell, H.-H. Lee, P. Yu, and H. Zaghouani
A Sudden Decline in Active Membrane-Bound TGF-{beta} Impairs Both T Regulatory Cell Function and Protection against Autoimmune Diabetes
J. Immunol., December 15, 2004; 173(12): 7308 - 7316.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
H.-Y. Qin, P. Chaturvedi, and B. Singh
In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-{gamma}/TNF-{alpha}
Int. Immunol., December 1, 2004; 16(12): 1723 - 1732.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
F. Fallarino, R. Bianchi, C. Orabona, C. Vacca, M. L. Belladonna, M. C. Fioretti, D. V. Serreze, U. Grohmann, and P. Puccetti
CTLA-4-Ig Activates Forkhead Transcription Factors and Protects Dendritic Cells from Oxidative Stress in Nonobese Diabetic Mice
J. Exp. Med., October 18, 2004; 200(8): 1051 - 1062.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. A. Salam, K. Matin, N. Matsumoto, Y. Tsuha, N. Hanada, and H. Senpuku
E2f1 Mutation Induces Early Onset of Diabetes and Sjogren's Syndrome in Nonobese Diabetic Mice
J. Immunol., October 15, 2004; 173(8): 4908 - 4918.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Sarween, A. Chodos, C. Raykundalia, M. Khan, A. K. Abbas, and L. S. K. Walker
CD4+CD25+ Cells Controlling a Pathogenic CD4 Response Inhibit Cytokine Differentiation, CXCR-3 Expression, and Tissue Invasion
J. Immunol., September 1, 2004; 173(5): 2942 - 2951.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Q.-S. Mi, D. Ly, P. Zucker, M. McGarry, and T. L. Delovitch
Interleukin-4 but not Interleukin-10 Protects Against Spontaneous and Recurrent Type 1 Diabetes by Activated CD1d-Restricted Invariant Natural Killer T-Cells
Diabetes, May 1, 2004; 53(5): 1303 - 1310.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. V. Serreze, T. M. Holl, M. P. Marron, R. T. Graser, E. A. Johnson, C. Choisy-Rossi, R. M. Slattery, S. M. Lieberman, and T. P. DiLorenzo
MHC Class II Molecules Play a Role in the Selection of Autoreactive Class I-Restricted CD8 T Cells That Are Essential Contributors to Type 1 Diabetes Development in Nonobese Diabetic Mice
J. Immunol., January 15, 2004; 172(2): 871 - 879.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
W. H. Schott, B. D. Haskell, H. M. Tse, M. J. Milton, J. D. Piganelli, C. M. Choisy-Rossi, P. C. Reifsnyder, A. V. Chervonsky, and E. H. Leiter
Caspase-1 Is Not Required for Type 1 Diabetes in the NOD Mouse
Diabetes, January 1, 2004; 53(1): 99 - 104.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. S. Riminton, R. Kandasamy, D. Dravec, A. Basten, and A. G. Baxter
Dermal Enhancement: Bacterial Products on Intact Skin Induce and Augment Organ-Specific Autoimmune Disease
J. Immunol., January 1, 2004; 172(1): 302 - 309.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Chen, W.-H. Lee, P. Yun, P. Snow, and C.-P. Liu
Induction of Autoantigen-Specific Th2 and Tr1 Regulatory T Cells and Modulation of Autoimmune Diabetes
J. Immunol., July 15, 2003; 171(2): 733 - 744.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
U. Grohmann, F. Fallarino, R. Bianchi, C. Orabona, C. Vacca, M. C. Fioretti, and P. Puccetti
A Defect in Tryptophan Catabolism Impairs Tolerance in Nonobese Diabetic Mice
J. Exp. Med., July 7, 2003; 198(1): 153 - 160.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. V. Serreze, M. A. Pierce, C. M. Post, H. D. Chapman, H. Savage, R. T. Bronson, P. B. Rothman, and G. A. Cox
Paralytic Autoimmune Myositis Develops in Nonobese Diabetic Mice Made Th1 Cytokine-Deficient by Expression of an IFN-{gamma} Receptor {beta}-Chain Transgene
J. Immunol., March 1, 2003; 170(5): 2742 - 2749.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. J. Quintana, P. Carmi, and I. R. Cohen
DNA Vaccination with Heat Shock Protein 60 Inhibits Cyclophosphamide-Accelerated Diabetes
J. Immunol., November 15, 2002; 169(10): 6030 - 6035.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. Tracy, K. M. Drescher, N. M. Chapman, K.-S. Kim, S. D. Carson, S. Pirruccello, P. H. Lane, J. R. Romero, and J. S. Leser
Toward Testing the Hypothesis that Group B Coxsackieviruses (CVB) Trigger Insulin-Dependent Diabetes: Inoculating Nonobese Diabetic Mice with CVB Markedly Lowers Diabetes Incidence
J. Virol., October 25, 2002; 76(23): 12097 - 12111.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Yu, G. C. Sharp, and H. Braley-Mullen
Dual Roles for IFN-{gamma}, But Not for IL-4, in Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice
J. Immunol., October 1, 2002; 169(7): 3999 - 4007.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J.-F. Bach
The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases
N. Engl. J. Med., September 19, 2002; 347(12): 911 - 920.
[Full Text] [PDF]

Home page
 JEMHome page
K. V. Tarbell, M. Lee, E. Ranheim, C. C. Chao, M. Sanna, S.-K. Kim, P. Dickie, L. Teyton, M. Davis, and H. McDevitt
CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer
J. Exp. Med., August 19, 2002; 196(4): 481 - 492.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
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]

Home page
 DiabetesHome page
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]

Home page
 DiabetesHome page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]

Home page
 J. Immunol.Home page
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]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2001 by The American Association of Immunologists, Inc. All rights reserved.