title: Deregulated MHC class II transactivator expression leads to a strong Th2 bias in CD4+ T lymphocytes.
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.
authors.affiliation: Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland. Luc.Otten@ib.unil.ch
authors.forename: Luc A
authors.initials: LA
authors.lastname: Otten
authors.forename: Fabienne
authors.initials: F
authors.lastname: Tacchini-Cottier
authors.forename: Michael
authors.initials: M
authors.lastname: Lohoff
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cosmi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scarpellino
authors.forename: Jacques
authors.initials: J
authors.lastname: Louis
authors.forename: Viktor
authors.initials: V
authors.lastname: Steimle
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
mesh_terms: D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000276:immunology*; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics
chemical_list: D016207:Cytokines; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators