A novel role for the major histocompatibility complex class II transactivator CIITA in the repression of IL-4 production.
Class II transactivator (CIITA) is known as a coactivator for MHC class II gene expression in antigen-presenting cells. Surprisingly, when CIITA-/- CD4 T cells were stimulated in the presence of IL-12, they produced not only IFNgamma but also high levels of IL-4. The IL-4 production is due to the accumulation of IL-4 gene transcripts in Th1 cells. This transcriptional control is observed in T cells differentiating to the Th1 but not Th2 lineage, consistent with induction of expression of the CIITA gene in T cells by IFNgamma. Thus, in addition to its role in transactivation of genes involved in antigen presentation, CIITA plays a critical role during the T cell differentiation by negatively regulating the IL-4 gene transcription.
Gourley
T
T
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109, USA.
Roys
S
S
Lukacs
N W
NW
Kunkel
S L
SL
Flavell
R A
RA
Chang
C H
CH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015769:Granuloma, Respiratory Tract / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019076:Transgenes / Q000235:genetics / Q000276:immunology
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D015847:Interleukin-4