Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium.

Role of T3 surface molecules in human T-cell activation: T3-dependent activation results in an increase in cytoplasmic free calcium.
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T3 表面分子在人类 T 细胞激活中的作用:T3 依赖性激活导致细胞质游离钙增加。

DOI:
10.1073/pnas.81.13.4169
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发表时间:
1984
影响因子:
11.1
通讯作者:
Stobo,J
Stobo,J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Weiss,A;Imboden,J;Shoback,D;Stobo,J

文献摘要

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用人T细胞白血病Jurkat和T_3阴性突变体Jurkat(S.5)研究了T_3在人T细胞活化中的作用。Jurkat与植物血凝素(PHA)孵育后产生白介素2,加入佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)可显著增加IL-2的产生。与T3反应的抗体只有在与PMA共同作用时才能激活Jurkat。然而,S.5细胞不能产生PHA反应的IL-2,并且产生Jurkat反应PHA和PMA所产生的IL-2活性的1/16。S5细胞与钙离子载体A23187和PMA孵育后产生的IL-2活性与Jurkat相当。与与T3反应的抗体一样,A23187显示了PMA激活Jurkat或S.5所必需的条件。这些观察表明,T3可能通过增加细胞内钙离子的机制参与T细胞的激活。这是通过使用钙敏感的荧光试剂Quin-2来测量细胞质内游离钙[(Ca~(2+)]i)来检测的。PHA、A23187或与T3反应的单抗作用于Jurkat细胞后,细胞内[Ca~(2+)]_i显著升高,而仅A23187可引起S_5细胞内[Ca~(2+)]_i升高。另外三种与Jurkat或S.5上表达的其他膜抗原反应的单抗不能升高[Ca~(2+)]_i。这些结果表明,T_3和/或相关分子通过导致[Ca~(2+)]_i升高的机制参与T细胞的激活,它们的表达是PHA激活T细胞的相对要求。
The human T-cell leukemia, Jurkat, and a T3-negative mutant of Jurkat (S.5) were used to study the role of T3 in human T-cell activation. Incubation of Jurkat with phytohemagglutinin (PHA) resulted in the production of interleukin 2, which was markedly increased by the addition of phorbol 12-myristate 13-acetate (PMA). Antibodies reactive with T3 could activate Jurkat only if added together with PMA. However, S.5 cells failed to produce interleukin 2 in response to PHA and produced 1/16th the interleukin 2 activity that Jurkat produced in response to PHA and PMA. Incubation of S.5 cells with the calcium ionophore A23187 and PMA resulted in the production of interleukin 2 activity comparable to that produced by Jurkat. Like antibodies reactive with T3, A23187 demonstrated an obligate requirement for PMA in order to activate Jurkat or S.5. These observations suggested that T3 might participate in T-cell activation through mechanisms that increase intracellular Ca2+. This was examined by using the Ca2+ sensitive fluor, quin-2, to measure levels of cytoplasmic free Ca2+ [( Ca2+]i). Addition of PHA, A23187, or monoclonal antibodies reactive with T3 to Jurkat cells resulted in substantial increases of [Ca2+]i. In contrast, only A23187 could induce an increase in [Ca2+]i in S.5 cells. Three other monoclonal antibodies reactive with other membrane antigens expressed on Jurkat or S.5 did not increase [Ca2+]i. These results suggest that T3 and/or associated molecules participate in T-cell activation through mechanisms that lead to increases in [Ca2+]i and that their expression is a relative requirement for T-cell activation by PHA.