Chung C D, Lewis L A, Miceli M C
Department of Microbiology and Immunology, University of California-Los Angeles School of Medicine, 90095, USA.
J Immunol. 1997 Aug 15;159(4):1758-66.
The T cell hybridoma BI-141 has been previously used to dissect the roles of Lck in Ag-induced IL-2 production. Here we demonstrate that BI-141 undergoes apoptosis in response to TCR stimulation using Ag or anti-TCR Abs. Using a panel of BI-141 transfectants expressing constitutively activated Lck (F505) or phosphotyrosine-binding (K154F505 and C156F505) or kinase-impaired (R273F505) mutants, we assess the relative requirements for Lck in TCR-mediated IL-2 production and apoptosis. While BI-141 transfectants expressing F505 are dramatically enhanced in their ability to produce IL-2 in response to Ag relative to K154F505-, C156F505-, or R273F505-expressing transfectants, no differences between these transfectants are observed in their ability to undergo TCR-induced apoptosis. TCR-induced Fas ligand (FasL) expression is demonstrated to be dependent on Lck SH2 and kinase activities, although FasL expression cannot be correlated with apoptosis. Low levels of Fas are constitutively expressed at equal levels on transfectants and are not increased in response to TCR ligation. Together, these data indicate that TCR-induced apoptosis in BI-141 is regulated through a mechanism(s) distinct from the Lck-induced expression of Fas, FasL, or IL-2 production. This TCR signal may be independent of Lck kinase and SH2 activities, or may require lower threshold activity. The identification of differential requirements for particular T cell functions is crucial to understanding how TCR engagement affects downstream T cell functions and may aid in the rational design of therapeutics aimed at specifically modulating particular T cell responses.
T细胞杂交瘤BI-141先前已被用于剖析Lck在抗原诱导的白细胞介素-2（IL-2）产生中的作用。在此，我们证明BI-141在使用抗原或抗T细胞受体（TCR）抗体进行TCR刺激时会发生凋亡。利用一组表达组成型活化Lck（F505）或磷酸酪氨酸结合（K154F505和C156F505）或激酶受损（R273F505）突变体的BI-141转染细胞，我们评估了Lck在TCR介导的IL-2产生和凋亡中的相对需求。虽然相对于表达K154F505、C156F505或R273F505的转染细胞，表达F505的BI-141转染细胞在响应抗原时产生IL-2的能力显著增强，但在这些转染细胞经历TCR诱导凋亡的能力方面未观察到差异。TCR诱导的Fas配体（FasL）表达被证明依赖于Lck的SH2和激酶活性，尽管FasL表达与凋亡无关。低水平的Fas在转染细胞上以相等水平组成型表达，并且在响应TCR连接时不会增加。总之，这些数据表明BI-141中TCR诱导的凋亡是通过一种不同于Lck诱导的Fas、FasL表达或IL-2产生的机制来调节的。这种TCR信号可能独立于Lck激酶和SH2活性，或者可能需要较低的阈值活性。确定特定T细胞功能的不同需求对于理解TCR结合如何影响下游T细胞功能至关重要，并且可能有助于合理设计旨在特异性调节特定T细胞反应的治疗方法。
