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Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytes

Otten, L. A.
Lohoff, Michael
Annunziato, Francesco
Cosmi, Lorenzo
Scarpellino, Leonardo
Louis, Jacques
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Published in Journal of Immunology. 2003, vol. 170, no. 3, p. 1150-1157
Abstract The MHC class II (MHC-II) transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC-II-restricted Ag presentation. Fine tuning of CIITA gene expression determines the cell type-specific expression of MHC-II genes. This regulation is achieved by the selective usage of multiple CIITA promoters. It has recently been suggested that CIITA also contributes to Th cell differentiation by suppressing IL-4 expression in Th1 cells. In this study, we show that endogenous CIITA is expressed at low levels in activated mouse T cells. Importantly CIITA is not regulated differentially in murine and human Th1 and Th2 cells. Ectopic expression of a CIITA transgene in multiple mouse cell types including T cells, does not interfere with normal development of CD4(+) T cells. However, upon TCR activation the CIITA transgenic CD4(+) T cells preferentially differentiate into IL-4-secreting Th2-type cells. These results imply that CIITA is not a direct Th1-specific repressor of the IL-4 gene and that tight control over the expression of CIITA and MHC-II is required to maintain the normal balance between Th1 and Th2 responses.
Keywords AdultAnimalsCD4-Positive T-Lymphocytes/cytology/ immunology/ metabolismCell Differentiation/genetics/immunologyCytokines/biosynthesisGene Expression Regulation/ immunologyGenes, MHC Class II/ geneticsHumansLymphocyte Activation/geneticsMiceMice, Inbred BALB CMice, Inbred C57BLMice, Inbred CBAMice, TransgenicNuclear ProteinsSpecies SpecificityTh1 Cells/immunology/metabolismTh2 Cells/ immunology/ metabolism/secretionTrans-Activators/ biosynthesis/ deficiency/genetics
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PMID: 12538670
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