佐々木 ひと美

The rejection of xenografts is characterized by infiltration of monocytes and natural killer (NK) cells into the graft, suggesting an important role for the innate immune system in xenorecognition. In this study, purified human NK or T cells were cocultured with porcine endothelial cells, and cytokines were analyzed by ELISA and intracellular FACS. We demonstrated a vigorous human anti-porcine xenoresponse that was associated with a strong T-cell proliferation against porcine endothelial cells. Limiting dilution cloning and T-cell receptor (TCR) Vbeta gene usage revealed a low number of xenoreactive T-cell precursors. We demonstrated that xenogeneic porcine but not allogeneic human endothelial cells induced the early production of interferon (IFN)-gamma by human NK cells but not by CD3+ T cells. Porcine xenoantigen-induced IFN-gamma production was only partially dependent on IL-12. Blocking IL-12 with neutralizing antibodies or by depletion of human macrophages partially decreased IFN-gamma production by CD56+ NK cells. Three-color flow cytometry revealed that IL-12 was produced through a species-specific activation of human macrophages by porcine endothelial cells. Our results indicate that the direct activation of NK cells and macrophages by porcine endothelial cells provides a unique pathway of xenorecognition that augments downstream specific T-cell immunity and represents a powerful effector mechanism in xenograft rejection.

献腎移植の術直後よりシクロスポリン,メチルプレドニゾロン,アザチオプリン,ALGを用い,腎機能回復後にアザチオプリンをミゾリビンに変更するプロトコールを用いた献腎移植80例の移植成績を検討した.WITは1〜52分,TITは325〜2603分,immediate functionは18例でprimary non functionは認められなかった.術後ATNを認めたdelayed graftfunction群の透析期間は1〜39日,最低血清クレアチニンは0.5〜3.8mg/dlであった.80例のうち10例はシクロスポリンの減量目的でミゾリビンからMMFに変更したが,5例はMMFの副作用でミゾリビンに変更した.10例はシクロスポリンの減量と食思不振を目的としてミゾリビンからMMF又はアザチオプリンに変更したが,5例は消化器症状,食思不振,血小板減少,嘔気,感染症等で再度ミゾリビンに変更した.生存率は1年97.5%,3年96.2%,5年93.0%,7年93.0%,腎生着率は1年97.5%,3年96.2%,5年88.3%,7年73.4%であった