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人γ/δ-TCR+淋巴因子激活的杀伤细胞对K562和Daudi细胞的异质性结合及杀伤行为。

Heterogeneous binding and killing behaviour of human gamma/delta-TCR+ lymphokine-activated killer cells against K562 and Daudi cells.

作者信息

Vollenweider I, Vrbka E, Fierz W, Groscurth P

机构信息

Institute of Anatomy, University of Zürich-Irchel, Switzerland.

出版信息

Cancer Immunol Immunother. 1993 May;36(5):331-6. doi: 10.1007/BF01741172.

Abstract

Effector-target conjugates, formed by coincubation of lymphokine-activated killer (LAK) cells with either K562 or Daudi cells, were separated from single cells by Percoll sedimentation. The occurrence of various CD molecules (CD3, CD56, CD57, CD16, gamma/delta-TCR) was compared in both fractions. Only LAK cells expressing the gamma/delta T cell receptor (TCR) were found in a significantly increased percentage in fractions containing conjugates indicating that gamma/delta-TCR+ LAK cells were preferably bound to target cells at the time of separation. In order to determine whether gamma/delta-TCR+ LAK cells also show a preferred killing activity against the targets, cultures enriched with or depleted of gamma/delta-TCR+ cells were established. Against K562 cells, gamma/delta-TCR(+)-enriched cultures showed a greatly reduced killing activity compared to LAK bulk cultures or cultures depleted of gamma/delta-TCR+ cells. Using Daudi cells as targets the enriched fraction revealed a slightly increased killing activity compared to bulk cultures or depleted fractions. Preincubation of gamma/delta-TCR+ LAK cells with anti-gamma/delta or anti-CD3 mAb resulted in a distinct increase of the killing activity against K562 cells, but in only a slightly enhanced activity against Daudi cells. It is postulated that gamma/delta-TCR+ LAK cells use the same adhesion mechanism for both targets but that only Daudi cells express a specific ligand for the gamma/delta-TCR. Occupation of the gamma/delta-TCR/CD3 complex by mAb, however, seems to substitute for the absent epitope on K562 cells by eliciting stimulatory signals in gamma/delta-TCR+LAK cells which, in combination with the binding stimulus, trigger cytolytic activity.

摘要

通过将淋巴因子激活的杀伤细胞(LAK细胞)与K562或Daudi细胞共同孵育形成的效应器-靶标结合物,通过Percoll沉降与单个细胞分离。比较了两个组分中各种CD分子(CD3、CD56、CD57、CD16、γ/δ-TCR)的出现情况。在含有结合物的组分中,仅发现表达γ/δT细胞受体(TCR)的LAK细胞百分比显著增加,这表明γ/δ-TCR+LAK细胞在分离时优先与靶细胞结合。为了确定γ/δ-TCR+LAK细胞是否也对靶标表现出优先杀伤活性,建立了富含或缺乏γ/δ-TCR+细胞的培养物。与LAK大量培养物或缺乏γ/δ-TCR+细胞的培养物相比,富含γ/δ-TCR(+)的培养物对K562细胞的杀伤活性大大降低。以Daudi细胞为靶标,与大量培养物或缺乏γ/δ-TCR+细胞的组分相比,富含γ/δ-TCR+细胞的组分显示出略有增加的杀伤活性。γ/δ-TCR+LAK细胞与抗γ/δ或抗CD3单克隆抗体预孵育导致对K562细胞的杀伤活性明显增加,但对Daudi细胞的活性仅略有增强。据推测,γ/δ-TCR+LAK细胞对两种靶标使用相同的粘附机制,但只有Daudi细胞表达γ/δ-TCR的特异性配体。然而,单克隆抗体占据γ/δ-TCR/CD3复合物似乎通过在γ/δ-TCR+LAK细胞中引发刺激信号来替代K562细胞上缺失的表位,这些信号与结合刺激相结合,触发细胞溶解活性。

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