Liu Y, Janeway C A
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.
J Exp Med. 1990 Dec 1;172(6):1735-9. doi: 10.1084/jem.172.6.1735.
We have used anti-T cell monoclonal antibodies (mAbs) as mimic ligands to study the effects of T cell receptor (TCR) ligation of cloned T helper type 1 cells in the presence or absence of accessory cells. Our results demonstrate that ligation of the TCR in the absence of accessory cells rapidly induces cell death. Cell death can be prevented by addition of spleen adherent cells, leading to strong clonal expansion. Induced cell death is inhibited by cyclosporin A and by anti-interferon gamma (IFN-gamma), and is restored by adding exogenous recombinant IFN-gamma to cyclosporin A-treated cells. These results demonstrate that IFN-gamma plays a critical role in cell death induced by anti-TCR mAbs in the absence of costimulatory cells. We propose that induced cell death of active effector T cells provides a third mechanism of tolerance in addition to intrathymic deletion of developing autoreactive T cells and peripheral inactivation of mature, naive T cells.
我们使用抗T细胞单克隆抗体（mAb）作为模拟配体，以研究在有或无辅助细胞存在的情况下，克隆的1型辅助性T细胞的T细胞受体（TCR）连接的影响。我们的结果表明，在没有辅助细胞的情况下，TCR的连接会迅速诱导细胞死亡。添加脾黏附细胞可预防细胞死亡，从而导致强烈的克隆扩增。环孢菌素A和抗干扰素γ（IFN-γ）可抑制诱导的细胞死亡，而向经环孢菌素A处理的细胞中添加外源性重组IFN-γ可恢复细胞死亡。这些结果表明，在没有共刺激细胞的情况下，IFN-γ在抗TCR mAb诱导的细胞死亡中起关键作用。我们提出，活性效应T细胞的诱导性细胞死亡提供了一种耐受性的第三种机制，这是除了发育中的自身反应性T细胞在胸腺内缺失和成熟幼稚T细胞在外周失活之外的机制。
