新しい免疫抑制剤の作用形式の検討

Abstract

FK506の作用をクローン化T細胞, HTL403とHTL805とを用いてCyclosporine (CsA)と比較検討した.表面抗原解析および機能分析により, HTL403はヘルパーT細胞, HTL805は細胞障害性T細胞である.HTL403のrIL2刺激による反応は高濃度のFK506でも抑制は軽度であった.またアロ刺激時のFK506による反応抑制はrIL2添加により, FK506の高濃度域で回復したがCsAと異なりrIL2単独刺激の水準までは回復しなかった.FK506は, HTL805のrIL2単独およびアロ, rIL2同時刺激による反応を低濃度から高濃度まで同程度に強く抑制した.とくにアロ抗原, rIL2同時刺激時の反応抑制率が高かったが, 高濃度域での抑制はCsAが強かった

We applied cloned human T lymphocytes established in our laboratory to evaluate the mode of action of Cyclosporine (CsA) and FK506. Phenotypic and functional analysis led us to conclude that HTL403 was a helper T cell clone and HTL805 a cytotoxic one. Susceptibility of HTL-403 to the immunosuppressants demonstrated that alloantigen-driven proliferative response can recover to the rIL2-driven level by the addition of rIL2 at higher concentration of the agents. Although full recovery was not observed in FK506, this finding indicated that FK506 as well as CsA inhibit IL2 secretion from HTL403. FK506 showed remarkable suppressive effect on the proliferative response of HTL-805 even at a considerably low concentration, while CsA suppressed such a response dose-dependently. We concluded that FK506 can be used to reverse ongoing acute rejection as well as to prevent acute rejection.