T cell expression of CIITA represses Th1 immunity.
Despite the fact that major histocompatibility complex class II transactivator (CIITA) has been known to be involved in Th1/Th2 balance in addition to its major role as a master regulator for the expression of MHC class II genes, the exact role of CIITA in Th1/Th2 balance is still controversial. To investigate whether the Th1/Th2 balance could be modulated by T cell specific expression of CIITA, we generated CIITA-transgenic mice, in which the CIITA expression is controlled by the distal promoter of p56lck, resulting in constitutive expression of CIITA predominantly in peripheral T cells. Naive CD4+ T cells from CIITA-transgenic mice exhibited a low level of IFN-gamma secretion as well as impaired Th1 polarization in vitro, while IL-4 secretion was enhanced under Th2 condition. In addition, the development of experimental autoimmune encephalomyelitis (EAE), a prototype of Th1-mediated disease, was repressed in CIITA-transgenic mice. Resistance to EAE was correlated with reduced production of IFN-gamma in response to MOG35-55, while the proliferation of MOG35-55 -specific T cells was not affected in CIITA-transgenic mice. Together, these data demonstrate that overexpression of CIITA in T cells inhibits Th1 differentiation and function, suggesting that the expression of CIITA in T cells might play a role in the regulation of the Th1/Th2 balance during the T cell lineage commitment.
Park
Weon Seo
WS
Department of Pathology, Kangwon University College of Medicine, Chunchon, Korea.
Bae
Youngmee
Y
Chung
Doo Hyun
DH
Choi
Yoon-La
YL
Kim
Byoung Kwon
BK
Sung
Young Chul
YC
Choi
Eun Young
EY
Park
Seong Hoe
SH
Jung
Kyeong Cheon
KC
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000096:biosynthesis*
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma