International Immunology Advance Access published online on October 11, 2006
International Immunology, doi:10.1093/intimm/dxl102
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1 Department of Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
* To whom correspondence should be addressed. Comparative studies using Th2-prone BALB/c and Th1-prone C57BL/6 mice were performed to clarify the influence of genetic background on Th cell differentiation. The results showed IL-4, the production of which is induced by IL-2, to be much more abundantly produced by BALB/c naive CD4+ T cells than by C57BL/6 naive CD4+ T cells, thereby leading to a tendency for differentiation toward Th2 in BALB/c naive CD4+ T cells. This difference in IL-4 production between the two naive CD4+ T cells appeared to be attributable to specific intracellular signaling events. Signal transducer and activator of transcription 5 (STAT5) was preferentially activated by IL-2 in CD4+ T cells developing in BALB/c in contrast to the corresponding cells in C57BL/6. In addition, IL-4 also induced stronger STAT5 activation in CD4+ T cells developing in BALB/c than in those developing in C57BL/6, whereas STAT6 was equally activated in these two cells. Further results supported the involvement of STAT5 in the difference in Th cell differentiation between BALB/c and C57BL/6 naive CD4+ T cells. STAT5A-/- naive CD4+ T cells with the BALB/c genetic background showed markedly less IL-2-induced IL-4 production than BALB/c naive CD4+ T cells. Conversely, forced expression of the constitutively active forms of STAT5A and STAT5B in C57BL/6 naive CD4+ T cells promoted the differentiation of Th2 cells. Thus, our results indicate IL-2-induced IL-4 production by naive CD4+ T cells, in which STAT5 activation is involved and directly controlled by the genetic background, to influence Th cell differentiation in murine strains.
Received June 22, 2006
Accepted September 13, 2006
Article
Genetic background influences Th cell differentiation by controlling the capacity for IL-2-induced IL-4 production by naive CD4+ T cells
Junji Yagi 1 *, Yutaka Arimura 2, Hiroaki Takatori 3, Hiroshi Nakajima 3, Itsuo Iwamoto 3, and Takehiko Uchiyama 4
2 Department of Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; Present address: Inflammatory and Infectious Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
3 Department of Allergy and Clinical Immunology, Chiba University School of Medicine, 1-8-1 Inohara, Chiba City, Chiba 260-8670, Japan
4 Department of Microbiology and Immunology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan; Institute of Laboratory Animals, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
Junji Yagi, E-mail: jyagi1{at}research.twmu.ac.jp
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