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

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

doi:10.4049/jimmunol.170.3.1150

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Title		Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytes
Authors		Otten, L. A. Tacchini-Cottier, Fabienne Lohoff, Michael Annunziato, Francesco Cosmi, Lorenzo Scarpellino, Leonardo Louis, Jacques Steimle, Viktor Reith, Walter Acha-Orbea, Hans show all authors [1 - 10]
Published in		The 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		Adult — Animals — CD4-Positive T-Lymphocytes/cytology/ immunology/ metabolism — Cell Differentiation/genetics/immunology — Cytokines/biosynthesis — Gene Expression Regulation/ immunology — Genes, MHC Class II/ genetics — Humans — Lymphocyte Activation/genetics — Mice — Mice, Inbred BALB C — Mice, Inbred C57BL — Mice, Inbred CBA — Mice, Transgenic — Nuclear Proteins — Species Specificity — Th1 Cells/immunology/metabolism — Th2 Cells/ immunology/ metabolism/secretion — Trans-Activators/ biosynthesis/ deficiency/genetics
Identifiers		DOI: 10.4049/jimmunol.170.3.1150 PMID: 12538670
Full text		Article - Limited access to UNIGE Other version: http://www.jimmunol.org/cgi/reprint/170/3/1150.pdf
Citation (ISO format)		OTTEN, L. A. et al. Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytes. In: The Journal of immunology, 2003, vol. 170, n° 3, p. 1150-1157. doi: 10.4049/jimmunol.170.3.1150 https://archive-ouverte.unige.ch/unige:11502