In vivo immunosuppression by derivatives of recombinant glycosylation inhibiting factor

T. Mikayama, I. Serizawa, M. Sato, T. Miura, T. Tomura, H. Watarai, N. Honma, N. Yuyama, M. Salo, Y. Takeuchi, N. Kubola, K. Ishizaka

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Abstract

We iiave previously described lhat suppressor T cell (Ts)-derivcd glycosylation inhibiting factor (GIF), a 13 kDa cylokine, suppressed in vivo antibody response. Since accumulating evidence suggested that conformationa! transition is involved in the generation of bioactive GIF by Ts, we generated bioactive recombinanl human GIF (recGIF) derivatives by mutations. Administration of recGIF derivative to DNP-OVA immunized BDFI mice resulted in suppression of the anti-DNP antibody response in a dose-dependent manner. When the recGIF was administered at the T cell priming with urea-denatured OVA, the anti-DNP antibody response to a booster injection of DNP-OVA was markedly suppressed. It was also found that proliferalive responses of splenic CD4F cells of OVA-primed mice to OVA was suppressed by the treatment of the donor with the recGIF at the priming immunization. The recGIF treatment at Oie time of a booster injection of DNP-OVA could not prevent the induction of anti-DNP antibody response but enhanced decline of the antibody tiler, and suppressed the antibody response to the next immunization of the same antigen. These results indicate that the in vivo immunosuppresive effects of GIF may be due not only to the inhibition of antigen-priming of T cells but also to Ihe induction of active suppression in the presence of antigen. When nonobase diabetic (NOD) mice were treated from 5 weeks of age with the recGIF, spontaneous diabetes was almost completely prpiccted. These results collectively suggest the possible approaches to the utilization of the recGIF derivtives for therapeutic purposes.

Original languageEnglish (US)
Pages (from-to)A1219
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Mikayama, T., Serizawa, I., Sato, M., Miura, T., Tomura, T., Watarai, H., Honma, N., Yuyama, N., Salo, M., Takeuchi, Y., Kubola, N., & Ishizaka, K. (1996). In vivo immunosuppression by derivatives of recombinant glycosylation inhibiting factor. FASEB Journal, 10(6), A1219.