| Co-Investigator(Kenkyū-buntansha) |
SATOMI Susumu Tohoku University, School of Medicine Professor, 医学部, 教授 (00154120)
SASAKI Takeshi Tohoku University, School of Medicine Professor, 医学部, 教授 (50110656)
ASAO Hironobu Tohoku University, School of Medicine, 医学部, 助手 (80250744)
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| Research Abstract |
Treatments for tissue transplantation immunity and sutoimmune disease require desirable immunosuppressant drugs which have little side effects. In this study, we have attempted to establish a methodology for suppression of IL-2 function which plays critical roles in immune responses. For this purpose, we firstly demonstrated the subunit structure of functional IL-2 receptors in human and murine. Functional murine IL-2 receptors consist of complexes containing all the three receptor subunits, alpha, beta and gamma chains, while functional human receptors consist of complexes containing all the three receptor subunits or the two subunits, beta and gamma chains. The murine beta and gamma complex has no ability to bind IL-2. The IL-2 receptor gamma chain has also been shown to be shared among receptors for IL-4, IL-7 and IL-9, suggesting that the gamma chain contributes to a variety of functions mediated by these cytokines in vivo.
We have examined effects of anti-alpha, -beta and-gamma chain monoclonal antibodies (mAbs) on skin transplantation mixed lymphocyte reaction in mice. Combination treatment with the three mAbs induced 70% suppression of allo-stimulated mixed lymphocyte reaction, and elongation of transplanted skin tissue suvival times from 3 to 22 days. However, single treatment with each mAb exhibited less effectiveness for such immunosuppression. These results indicated that the mAbs specific for the three subunits of IL-2 receptors have immunosuppressive effects, suggesting a possible development of immunosuppressant drugs using the mAbs.
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