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International Immunology, Vol. 11, No. 12, 1873-1880, December 1999
© 1999 Japanese Society for Immunology

Increased c-Fos/activator protein-1 confers resistance against anergy induction on antigen-specific T cell

Hiroki Kawasaki11,2, Yukiko Nakata3, Gen Suzuki3, Kazuo Chihara2, Takeshi Tokuhisa4 and Shunichi Shiozawa1,2

1 Faculty of Health Science and
2 Department of Medicine, Third Division, Kobe University School of Medicine, Kobe 654, Japan
3 Division of Radiation Health, National Institute of Radiological Sciences, Chiba 263 8555, Japan
4 Division of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba 260 8670, Japan

Correspondence to: S. Shiozawa, Kobe University School of Medicine, Faculty of Health Science, 7-10-2 Tomogaoka, Sumaku, Kobe 654-0142, Japan

We have studied the contribution of c-Fos/activator protein-1 (AP-1) to antigen-specific T cell response with reference to T cell anergy by increasing c-Fos/AP-1 in vivo and in vitro. First, after injection of a high dose of staphylococcus enterotoxin B (SEB), clonal deletion of SEB-reactive Vß8+ CD4 T cells occurred both in control B6 and H2-c-fos transgenic (fos) mice, whereas proliferation of T cells against SEB was profoundly depressed in B6 but not in fos mice. Second, the keyhole limpet hemocyanin-specific CD4 Th1 cell clone produced decreasing amounts of IL-2 in response to increasing amounts of concanavalin A (Con A) in vitro, whereas the decrease was less significant in the Th1 clones stably transfected with c-fos gene. Electrophoretic mobility shift assay with nuclear protein from the transformants showed that overexpression of the c-fos gene compensated the amounts of AP-1 in the nuclei of Con A-treated Th1 clones. Thus, increased c-Fos/AP-1 confers resistance against anergy induction on antigen-specific T cells.

Keywords: activator protein-1, anergy, antigen-specific T cell, c-fos/c-Fos, IL-2

Transmitting editor: C. Martinez-A


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