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通过趋化因子依赖和非依赖机制刺激初始T细胞黏附和免疫突触形成。

Stimulation of naïve T-cell adhesion and immunological synapse formation by chemokine-dependent and -independent mechanisms.

作者信息

Bromley Shannon K, Dustin Michael L

机构信息

Graduate Program in Immunology, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Immunology. 2002 Jul;106(3):289-98. doi: 10.1046/j.1365-2567.2002.01441.x.

Abstract

Chemokines adsorbed to the cell surface play an important role in the initial interactions of T cells with endothelial cells, and may also have a role in T-cell interactions with dendritic cells. Therefore, we examined the effect of surface-adsorbed chemokines on the interaction of naïve murine splenic T cells with supported bilayers containing intercellular adhesion molecule (ICAM)-1, or with bone marrow-derived cultured dendritic cells in the presence and absence of relevant MHC-peptide complexes. Naïve T cells formed immunological synapses, defined as a ring of lymphocyte function associated (LFA)-1-ICAM-1 interactions surrounding a central cluster of MHC-peptide complexes, on supported planar bilayers containing ICAM-1 and relevant MHC-peptide complexes. Chemokines stimulated an increase in the percentage of naïve cells that adhered to ICAM-1, but did not increase the average number of LFA-1-ICAM-1 interactions in the contact area. In contrast, relevant MHC-peptide complexes resulted in a small increase in the proportion of interacting T cells, but stimulated an 8-fold increase in the number of LFA-1-ICAM-1 interactions in each contact formed. Naïve T cells displayed a significant basal adhesion to bone marrow dendritic cells that was further increased when relevant chemokines were adsorbed to the dendritic cell surface. However, basal and antigen-stimulated T-cell adhesion to dendritic cells was not sensitive to pertussis toxin. Thus, there are chemokine-independent mechanisms that initiate adhesion between T cells and dendritic cells.

摘要

吸附在细胞表面的趋化因子在T细胞与内皮细胞的初始相互作用中发挥重要作用,并且可能在T细胞与树突状细胞的相互作用中也起作用。因此,我们研究了表面吸附的趋化因子对未成熟小鼠脾T细胞与含有细胞间黏附分子(ICAM)-1的支持双层膜相互作用的影响,以及在存在和不存在相关主要组织相容性复合体(MHC)-肽复合物的情况下对未成熟小鼠脾T细胞与骨髓来源的培养树突状细胞相互作用的影响。在含有ICAM-1和相关MHC-肽复合物的支持平面双层膜上,未成熟T细胞形成了免疫突触,定义为围绕MHC-肽复合物中央簇的淋巴细胞功能相关(LFA)-1-ICAM-1相互作用环。趋化因子刺激了黏附到ICAM-1上的未成熟细胞百分比增加,但没有增加接触区域中LFA-1-ICAM-1相互作用的平均数量。相比之下,相关的MHC-肽复合物导致相互作用的T细胞比例略有增加,但刺激了每个形成的接触中LFA-1-ICAM-1相互作用数量增加8倍。未成熟T细胞对骨髓树突状细胞表现出显著的基础黏附,当相关趋化因子吸附到树突状细胞表面时,这种黏附进一步增加。然而,基础和抗原刺激的T细胞对树突状细胞的黏附对百日咳毒素不敏感。因此,存在不依赖趋化因子的机制启动T细胞与树突状细胞之间的黏附。

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