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International Immunology, Vol. 11, No. 7, 1149-1156, July 1999
© 1999 Japanese Society for Immunology

Target cells for an immunosuppressive cytokine, glycosylation-inhibiting factor

Katsuji Sugie1,2, Takafumi Tomura3, Kenji Takakura4, Tetsu Kawano5, Masaru Taniguchi5, Howard M. Grey2 and Kimishige Ishizaka1

1 Division of Immunobiology and
2 Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
3 Kirin Pharmaceutical Laboratory, Takasaki 370-12, Japan
4 Department of Obstetrics and Gynecology, Shiga University of Medical Science, Shiga 520-21, Japan
5 Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

Correspondence to: K. Ishizaka

Receptors for bioactive glycosylation-inhibiting factor (GIF) were demonstrated using a bioactive mutant of recombinant human (rh) GIF, which is comparable to the suppressor T (Ts) cell-derived bioactive GIF in its affinity for the receptors on helper T (Th) hybridoma cells. Both naive T and B cells in normal mouse spleen lacked GIF receptors. However, presentation of specific antigen to naive T cells resulted in the expression of the receptors on activated T cells. Furthermore, activation of small resting B cells with F(ab')2 fragments of anti-mouse IgM plus IL-4, lipopolysaccharide (LPS) plus IL-4 or LPS plus dextran sulfate induced the expression of the receptors within 48 h of B cell stimulation. It was also found that NK T cells freshly isolated from mouse spleen, but not conventional NK cells, expressed receptors for GIF. CD4+ and CD4 subpopulations of NK T cells showed a similar binding capability. Mature dendritic cells derived from bone marrow did not bear the receptors. The dissociation constant (Kd) of the interaction between the bioactive rhGIF mutant and the high-affinity receptors was 10–100 pM, whereas inactive wild-type rhGIF failed to bind to the receptors. A bioactive derivative of rhGIF suppressed both IgG1 and IgE synthesis by purified B cells activated by LPS and IL-4, indicating that the binding of bioactive GIF to its receptors on activated B cells results in suppression of their differentiation.

Keywords: cytokine receptor, Ig

Transmitting editor: T. Sasazuki


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