T cell expression of CIITA represses Th1 immunity

• Published in: International immunology 2004-10, Vol.16 (10), p.1355-1364
• Main Authors: Park, Weon Seo, Bae, Youngmee, Chung, Doo Hyun, Choi, Yoon-La, Kim, Byoung Kwon, Sung, Young Chul, Choi, Eun Young, Park, Seong Hoe, Jung, Kyeong Cheon
• Format: Article
• Language: English
• Subjects: Animals; APC antigen-presenting cell; B6 mice C57BL/6 mice; CBP CREB binding protein; Cell Differentiation - immunology; Cell Lineage - immunology; CIITA MHC class II transactivator; dTg double transgenic; EAE experimental autoimmune encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - immunology; Enzyme-Linked Immunosorbent Assay; experimental autoimmune encephalomyelitis; Flow Cytometry; Histocompatibility Antigens Class II - immunology; Humans; IFA incomplete Freund's adjuvant; IFN-γ; Immunity, Innate; Interferon-gamma; MHC class II; Mice; Mice, Transgenic; Nuclear Proteins - biosynthesis; PBS phosphate-buffered saline; Polymerase Chain Reaction; PPD purified protein derivative; Promoter Regions, Genetic; TCR T cell receptor; Th1 Cells - cytology; Th1 Cells - immunology; Th2 Cells - immunology; Trans-Activators - biosynthesis; transgenic mouse
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/dxh132

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-γ 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-γ 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.