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

Otten, Luc A.; Tacchini-Cottier, Fabienne; Lohoff, Michael; Annunziato, Francesco; Cosmi, Lorenzo; Scarpellino, Leonardo; Louis, Jacques; Steimle, Viktor; Reith, Walter; Acha-Orbea, Hans

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

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Steimle, Viktor
Spemann Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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引用

Otten, L. A., Tacchini-Cottier, F., Lohoff, M., Annunziato, F., Cosmi, L., Scarpellino, L., Louis, J., Steimle, V., Reith, W., & Acha-Orbea, H. (2003). Deregulated MHC Class II Transactivator Expression Leads to a Strong Th2 Bias in CD4^₊ T Lymphocytes. Journal of Immunology, 170(3), 1150-1157.

引用: https://hdl.handle.net/11858/00-001M-0000-002B-9576-4

要旨

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.