Glickstein L, Macphail S, Stutman O
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York 10021.
J Immunol. 1996 Mar 15;156(6):2062-7.
T cells may discriminate between stimuli in a variety of ways, including the presence of cytokines or other costimulatory signals, the type of Ag (peptide, superantigen, or allorecognition), or the magnitude of the signal through the TCR. We have used anti-CD3 stimulation of T hybridomas to examine signals generated through the TCR in the absence of exogenous APCs. Soluble whole anti-CD3, but not F(ab')2 anti-CD3, was able to stimulate the T hybridomas to produce IL-2. Plastic-bound anti-CD3, in contrast, stimulated TNF production, G1 arrest, and apoptosis by the T hybridoma. Engagement of the CD4 coreceptor on these cells had no effect on the overall pattern of signaling observed. Although TNF production was correlated with apoptosis, anti-TNF treatment did not prevent cell death or G1 arrest. The response of the T hybridoma to both forms of anti-CD3 included significant IL-2 production even at the lowest dose tested. However, soluble anti-CD3 at the highest dose tested elicited only minor apoptosis, while plastic-bound anti-CD3 elicited significant apoptosis even at the lowest dose. The difference in response was not evident at the level of phosphotyrosine proteins two min after cross-linking of the TCR.
T细胞可以通过多种方式区分刺激，包括细胞因子或其他共刺激信号的存在、抗原类型（肽、超抗原或同种异体识别），或通过TCR的信号强度。我们利用抗CD3刺激T杂交瘤，以研究在没有外源性抗原呈递细胞（APC）的情况下通过TCR产生的信号。可溶性全抗CD3，而不是F(ab')2抗CD3，能够刺激T杂交瘤产生白细胞介素-2（IL-2）。相比之下，塑料结合的抗CD3刺激T杂交瘤产生肿瘤坏死因子（TNF）、导致G1期停滞和凋亡。这些细胞上CD4共受体的结合对观察到的整体信号模式没有影响。尽管TNF的产生与凋亡相关，但抗TNF治疗并不能阻止细胞死亡或G1期停滞。T杂交瘤对两种形式抗CD3的反应，即使在测试的最低剂量下也包括显著的IL-2产生。然而，测试的最高剂量的可溶性抗CD3仅引起轻微凋亡，而塑料结合的抗CD3即使在最低剂量下也引起显著凋亡。在TCR交联两分钟后，磷酸酪氨酸蛋白水平上的反应差异并不明显。
