HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Koarada, S. Articles by Ridgway, W. M. Search for Related Content PubMed PubMed Citation Articles by Koarada, S. Articles by Ridgway, W. M.

Increased Entry into the IFN- Effector Pathway by CD4⁺ T Cells Selected by I-A^g7 on a Nonobese Diabetic Versus C57BL/6 Genetic Background¹

Division of Rheumatology and Immunology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261

IFN--mediated Th1 effects play a major role in the pathogenesis of autoimmune diabetes in nonobese diabetic (NOD) mice. We analyzed functional responses of CD4⁺ T cells from NOD and B6.G7 MHC congenic mice, which share the H2^g7 MHC region but differ in their non-MHC genetic background. T cells from each strain proliferated equally to panstimulation with T cell lectins as well as to stimulation with glutamic acid decarboxylase 524–543 (self) and hen egg lysozyme 11–23 (foreign) I-A^g7-binding peptide epitopes. Despite comparable proliferative responses, NOD CD4⁺ T cells had significantly increased IFN- intracellular/extracellular protein and mRNA responses compared with B6.G7 T cells as measured by intracellular cytokine analysis, time resolved fluorometry, and RNase protection assays. The increased IFN- production was not due to an increase in the amount of IFN- produced per cell but to an increase in the number of NOD CD4⁺ T cells entering the IFN--producing pathway. The increased IFN- response in NOD mice was not due to increased numbers of activated precursors as measured by activation/memory markers. B6.G7 lymphoid cells demonstrated an absolute decrease in IFN- mRNA, an increase in IL-4 mRNA production, and a significantly decreased IFN-:IL-4 mRNA transcript ratio compared with NOD cells. CD4⁺ T cells from C57BL6 mice also showed significantly decreased IFN- production compared with CD4⁺ T cells from NOD.H2^b MHC-congenic mice (which have an H2^b MHC region introgressed onto an NOD non-MHC background). Therefore, the NOD non-MHC background predisposes to a quantitatively increased IFN- response, independent of MHC class II-mediated T cell repertoire selection, even when compared with a prototypical Th1 strain.

This article has been cited by other articles:

				J. Irie, B. Reck, Y. Wu, L. S. Wicker, S. Howlett, D. Rainbow, E. Feingold, and W. M. Ridgway Genome-Wide Microarray Expression Analysis of CD4+ T Cells from Nonobese Diabetic Congenic Mice Identifies Cd55 (Daf1) and Acadl as Candidate Genes for Type 1 Diabetes J. Immunol., January 15, 2008; 180(2): 1071 - 1079. [Abstract] [Full Text] [PDF]

				S. Koarada, Y. Haruta, M. Mitamura, F. Morito, Y. Tada, A. Ohta, and K. Nagasawa Ex vivo CD4 + T-cell cytokine expression from patients with Sjogren's syndrome following in vitro stimulation to induce proliferation Rheumatology, April 1, 2006; 45(4): 392 - 399. [Abstract] [Full Text] [PDF]

				A. Ueno, S. Cho, L. Cheng, Z. Wang, B. Wang, and Y. Yang Diabetes Resistance/Susceptibility in T Cells of Nonobese Diabetic Mice Conferred by MHC and MHC-Linked Genes J. Immunol., October 15, 2005; 175(8): 5240 - 5247. [Abstract] [Full Text] [PDF]

				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]

				W. Zhou, S. Chang, and T. M. Aune From the Cover: Long-range histone acetylation of the Ifng gene is an essential feature of T cell differentiation PNAS, February 24, 2004; 101(8): 2440 - 2445. [Abstract] [Full Text] [PDF]

				S. Trembleau, G. Penna, S. Gregori, N. Giarratana, and L. Adorini IL-12 Administration Accelerates Autoimmune Diabetes in Both Wild-Type and IFN-{gamma}-Deficient Nonobese Diabetic Mice, Revealing Pathogenic and Protective Effects of IL-12-Induced IFN-{gamma} J. Immunol., June 1, 2003; 170(11): 5491 - 5501. [Abstract] [Full Text] [PDF]

				W. Zhou, F. Zhang, and T. M. Aune Either IL-2 or IL-12 Is Sufficient to Direct Th1 Differentiation by Nonobese Diabetic T Cells J. Immunol., January 15, 2003; 170(2): 735 - 740. [Abstract] [Full Text] [PDF]

				S. Koarada, Y. Wu, G. Olshansky, and W. M. Ridgway Increased Nonobese Diabetic Th1:Th2 (IFN-{gamma}:IL-4) Ratio Is CD4+ T Cell Intrinsic and Independent of APC Genetic Background J. Immunol., December 1, 2002; 169(11): 6580 - 6587. [Abstract] [Full Text] [PDF]

				I. Djilali-Saiah, P. Lapierre, S. Vittozi, and F. Alvarez DNA Vaccination Breaks Tolerance for a Neo-Self Antigen in Liver: A Transgenic Murine Model of Autoimmune Hepatitis J. Immunol., November 1, 2002; 169(9): 4889 - 4896. [Abstract] [Full Text] [PDF]