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International Immunology, Vol. 14, No. 6, pp. 555-566, June 2002
© 2002 Japanese Society for Immunology

A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulates their responses

Yutaka Arimura1, Hidehito Kato1, Umberto Dianzani4, Toshihiro Okamoto2, Soichiro Kamekura1, Donatella Buonfiglio4, Tohru Miyoshi-Akiyama1, Takehiko Uchiyama1,3 and Junji Yagi1

Departments of 1 Microbiology and Immunology, and 2 Oral and Maxillofacial Surgery, and 3 Institute of Laboratory Animals, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan 4 Laboratory of Immunology, Department of Medical Science, A. Avogadro University of Eastern Piedmont, 28100 Novara, Italy

Correspondence to: J. Yagi; E-mail: jyagi1{at}research.twmu.ac.jp
Transmitting editor: S. Koyasu

We examined the co-stimulatory activity of H4/ICOS on murine activated CD4+ T cells and found that the cross-linking of H4/ICOS enhanced their proliferation, in addition to raising IFN-{gamma}, IL-4 and IL-10 production to levels comparable to those induced by CD28. However, IL-2 production was only marginally co-stimulated by H4/ICOS. This distinct pattern of lymphokine production appears to be induced by a specific intracellular signaling event. Compared with CD28, H4/ICOS dominantly elicited the Akt pathway via phosphatidylinositol 3-kinase. In addition, mitogen-activated protein kinase family kinases were activated in different ways by CD28 and H4/ICOS. The strong phosphorylation of p46 c-Jun N-terminal kinase was observed upon CD28 co-stimulation, but was less potently induced by H4/ICOS. The strain diversity in the induction of H4/ICOS was recognized. The expression of H4/ICOS on BALB/c activated CD4+ T cells was >6-fold higher compared with C57BL/6 activated CD4+ T cells. Furthermore, BALB/c activated CD4+ T cells exhibited more Th2-deviated lymphokine production as compared with C57BL/6 activated CD4+ T cells and signaling through H4/ICOS during the primary stimulation of naive CD4+ T cells promoted the generation of Th2 cells. Thus, the difference in H4/ICOS expression on activated CD4+ T cells, which is regulated among the mouse strains, may also regulate the polarization of Th cells.

Keywords: immunoregulation, inducible co-stimulator, signal transduction, Th2 cells


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