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The Role of Accessory Cells in the Induction of Receptor-Mediated Human T Cell Growth.

辅助细胞在受体介导的人类 T 细胞生长诱导中的作用。

基本信息

批准号：
01480193
负责人：
KAKIMOTO Kiichi
金额：
$ 3.9万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480193/
关键词：
Accessory cell function T-macrophage interaction T cell proliferation Interferon-gamma Sur face-interaction molecules LFA-1 ICAM-1 LFAー1 細胞間相互作用マクロ-ファ-ジ ICAMー1 γーインタ-フェロン T細胞増殖

项目摘要

The present study was performed to made clear at molecular level the functions of accessory cells (AC) mediated by soluble factors released from AC and by cell-surface interaction between AC and T cells which are required for the induction of receptor-mediated human T cell proliferation.To dissect the AC functions into factor-mediated and cell contact-mediated functions, the AC-depleted peripheral blood (PB)-T cells were stimulated with anti-CD3-antibody coated on latex beads in a culture with or without macrophagederived soluble factors and paraformaldehyde (PFA)-fixed macrophages (f-Mo) and the T cell proliferation was examined. Major findings obtained in this study are summarized as follows.1) Both the factor-mediated and cell-contact-mediated accessory functions are required for the induction of the T cell proliferation.2) The soluble factors required were found to be IL-1 and IL-6. Both of these factors are indispensable because addition of either one of recombinant IL-1beta or IL … More -6 alone did not induce T cell proliferation, and the activity of Monoculture supernatant were diminished by adding either one of the neutralizing antibodies to IL-1beta or IL-6.3) A significant discovery in this study is that, before PFA-fixation, the macrophages had to be cultured with Con A-stimulated PB-mononuclear cells or interferon-gamma (IFN-gamma) to induce T cell proliferation. These results indicate that the expression of a certain cell-surface molecule (s) is induced by T cell-derived lymphokine (IFN-gamma) and this molecule is essential for the AC-T cell interaction.4) For AC-T cell interaction, inhibition studies with monoclinal antibodies (mAb) showed that interaction through LFA-1 and ICAM-1 is essential. In addition, a 200 Kd pan-leukocyte antigen was also shown to contribute significantly. This molecule is recognized by a mAd KW-23, raised in this study and appears to be a novel cell-interaction molecule.Thus our study demonstrated the dynamic bi-directional interaction between Mo and T cells. We proposed that, during the interaction, at least one of the necessary cell-interaction molecule is induced by IFN-gamma released from T cells. The Mo-T cell-interaction and soluble factors (IL-1 and IL-6) released from Mo induce IL-2 production and T cell proliferation. Less

本研究从分子水平阐明了辅助细胞（AC）的功能，即AC释放的可溶性因子介导的AC功能和AC与T细胞表面相互作用介导的AC功能，并将AC功能分为因子介导的AC功能和细胞接触介导的AC功能。在有或没有巨噬细胞衍生的可溶性因子和多聚甲醛（PFA）固定的巨噬细胞（f-Mo）的培养物中，用包被在乳胶珠上的抗CD 3抗体刺激AC耗尽的外周血（PB）-T细胞，并检测T细胞增殖。本研究的主要结果如下：1）因子介导的和细胞接触介导的辅助功能都是诱导T细胞增殖所必需的; 2）所需的可溶性因子是IL-1和IL-6。这两个因素都是不可缺少的，因为添加重组IL-1 β或IL-10中的任何一种， ...更多信息 3）本研究的一个重要发现是，在PFA固定之前，巨噬细胞必须与Con A刺激的PB-单核细胞或干扰素-γ（IFN-γ）一起培养以诱导T细胞增殖。这些结果表明，T细胞衍生的淋巴因子（IFN-γ）诱导某种细胞表面分子的表达，并且该分子对于AC-T细胞相互作用是必需的。4）对于AC-T细胞相互作用，单克隆抗体（mAb）的抑制研究表明，通过LFA-1和ICAM-1的相互作用是必需的。此外，200 Kd的泛白细胞抗原也显示出显著贡献。该分子被本研究中提出的mAd KW-23所识别，似乎是一种新的细胞相互作用分子，因此我们的研究证明了Mo和T细胞之间的动态双向相互作用。我们提出，在相互作用过程中，至少有一种必要的细胞相互作用分子是由T细胞释放的IFN-γ诱导的。Mo与T细胞的相互作用和Mo释放的可溶性因子（IL-1和IL-6）诱导IL-2产生和T细胞增殖。少