Deregulated MHC Class II Transactivator Expression Leads to a Strong Th2 Bias in CD4 super(+) T Lymphocytes

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 m...

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Veröffentlicht in:The Journal of immunology (1950) 2003-02, Vol.170 (3), p.1150-1157
Hauptverfasser: Otten, LA, Tacchini-Cottier, F, Lohoff, M, Annunziato, F, Cosmi, L, Scarpellino, L, Louis, J, Steimle, V, Reith, W, Acha-Orbea, H
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Sprache:eng
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Zusammenfassung: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 super(+) T cells. However, upon TCR activation the CIITA transgenic CD4 super(+) 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.
ISSN:0022-1767