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重组白细胞介素2诱导人循环自然杀伤细胞和T淋巴细胞增殖:白细胞介素1和白细胞介素2的协同作用

rIL 2-induced proliferation of human circulating NK cells and T lymphocytes: synergistic effects of IL 1 and IL 2.

作者信息

Ben Aribia M H, Leroy E, Lantz O, Métivier D, Autran B, Charpentier B, Hercend T, Senik A

出版信息

J Immunol. 1987 Jul 15;139(2):443-51.

PMID:3110271
Abstract

Cells participating in the rIL 2-induced proliferation of resting PBMC were identified by using different methods of cell purification. NK cells recovered in the light density fraction of Percoll gradients responded, as already known, directly to rIL 2 by strong proliferation. In contrast, large T lymphocytes co-purifying with NK cells, and small T cells sedimenting in the high density area of the Percoll gradients, were virtually unresponsive when cultivated in the sole presence of rIL 2. However, the addition of either irradiated autologous monocytes or highly purified IL 1 allowed both kinds of T cells to undergo cell division. Stringent elimination of possibly contaminating NK cells (NKH-1+) and/or activated T cells (TNKTAR, Tac+, HLA-DR+) from the high density T cells by complement lysis did not impair rIL 2-induced cell proliferation, indicating entire responsiveness of these cells to the synergistic action of IL 1 plus IL 2. Both high density CD4+ and CD8+ participated in this phenomenon, with an apparent advantage for CD4+ cells. All Tac+ cells emerging in a 6-day culture of these cells expressed the WT31 antigen, which indicates that T cells involved in rIL 2-induced proliferation are conventional mature T cells. The relative precursor frequencies of NK cells, large T lymphocytes, and small T lymphocytes that proliferated in response to rIL 2 were analyzed by limiting dilution analysis. The frequencies of clonal growth of NK cells and low density T lymphocytes were approximately the same (1/103 vs 1/185), whereas that of high density T cells was four times lower (1/458). Thus, we clearly demonstrate that resting T cells, defined as such by morphological, density, and phenotypic criteria, are able to proliferate in response to IL 2 in the presence of IL 1 without antigenic or mitogenic triggering.

摘要

通过使用不同的细胞纯化方法,鉴定了参与重组白细胞介素2(rIL 2)诱导的静息外周血单个核细胞(PBMC)增殖的细胞。如已知的那样,在Percoll梯度的低密度组分中回收的自然杀伤(NK)细胞通过强烈增殖直接对rIL 2作出反应。相比之下,与NK细胞共同纯化的大T淋巴细胞以及在Percoll梯度的高密度区域沉降的小T细胞,在仅存在rIL 2的情况下培养时几乎没有反应。然而,添加照射过的自体单核细胞或高度纯化的白细胞介素1(IL 1)可使这两种T细胞都进行细胞分裂。通过补体裂解从高密度T细胞中严格消除可能污染的NK细胞(NKH-1+)和/或活化的T细胞(TNKTAR、Tac+、HLA-DR+)并不损害rIL 2诱导的细胞增殖,这表明这些细胞对IL 1加IL 2的协同作用具有完全反应性。高密度的CD4+和CD8+细胞都参与了这一现象,其中CD4+细胞具有明显优势。在这些细胞的6天培养中出现的所有Tac+细胞都表达WT31抗原,这表明参与rIL 2诱导增殖的T细胞是传统的成熟T细胞。通过有限稀释分析来分析对rIL 2作出反应而增殖的NK细胞、大T淋巴细胞和小T淋巴细胞的相对前体细胞频率。NK细胞和低密度T淋巴细胞的克隆生长频率大致相同(1/103对1/185),而高密度T细胞的克隆生长频率则低四倍(1/458)。因此,我们清楚地证明,根据形态、密度和表型标准定义的静息T细胞能够在没有抗原或有丝分裂触发的情况下,在IL 1存在时对IL 2作出反应而增殖。

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