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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
Author(s) -
Chen XiaoPing,
Falkner Dewayne H.,
Morel Penelope A.
Publication year - 2005
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200425483
Subject(s) - biology , nod , cd8 , production (economics) , microbiology and biotechnology , immunology , genetics , gene , immune system , macroeconomics , economics
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.