Cellular immune response

Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter

  1. Xiao-Ping Chen1,3,
  2. Dewayne H. Falkner1,
  3. Penelope A. Morel1,2,*

Article first published online: 15 APR 2005

DOI: 10.1002/eji.200425483

Issue

European Journal of Immunology

European Journal of Immunology

Volume 35, Issue 5, pages 1408–1417, May 2005

Additional Information

How to Cite

Chen, X.-P., Falkner, D. and Morel, P. (2005), Impaired IL-4 production by CD8+ T cells in NOD mice is related to a defect of c-Maf binding to the IL-4 promoter. European Journal of Immunology, 35: 1408–1417. doi: 10.1002/eji.200425483

Author Information

  1. 1

    Department of Immunology, University of Pittsburgh, Pittsburgh, USA

  2. 2

    Department of Medicine, University of Pittsburgh, Pittsburgh, USA

  3. 3

    Department of Microbiology and Immunology, TongJi University School of Medicine, 1239 Si Pin Rd, Shanghai, P.R. China 200092

*Department of Immunology, University of Pittsburgh, 200 Lothrop Street, BST E1048, Pittsburgh, PA 15261, USA

Publication History

  1. Issue published online: 22 APR 2005
  2. Article first published online: 15 APR 2005
  3. Manuscript Accepted: 14 MAR 2005
  4. Manuscript Revised: 8 MAR 2005
  5. Manuscript Received: 16 JUL 2004

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Keywords:

  • Th1/Th2;
  • Autoimmunity;
  • Cytokines;
  • Transcription factors

Abstract

CD8+ T cells play an important role in the induction of the autoimmune response in non-obese diabetic (NOD) mice. Here we describe abnormalities in the control of cytokine production by NOD CD8+ T cells. NOD CD8+ T cells had an increased propensity to produce IFN-γ upon TCR activation, in both adult and 2-week-old mice. NOD CD8+ T cells had a reduced capacity to produce IL-4 in type 2 conditions compared to CD8+ T cells from the diabetes-resistant strains BALB/c and C57BL/6. Both GATA-3 and c-Maf, two positive transactivators for IL-4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8+ T cells. The GATA-3 was functional since normal levels of IL-5 were produced and the IL-4 promoter was hyperacetylated in NOD CD8+ T cells. In contrast, c-Maf failed to bind to its responsive element as determined by chromatin immunoprecipitation (ChIP) assay. These results suggest that NOD CD8+ T cells possess an increased propensity to produce IFN-γ and impaired c-Maf-dependent DNA binding activities in vivo that lead to reduced IL-4 production following TCR activation. These defects may facilitate the development of the autoimmune response by inducing an overall type 1-biased immune response in NOD mice.

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