Evidence implicating utilization of different T cell receptor-associated signaling pathways by TH1 and TH2 clones.
Evidence implicating utilization of different T cell receptor-associated signaling pathways by TH1 and TH2 clones.
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DOI：
10.4049/jimmunol.144.11.4110
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发表时间：
1990-06
影响因子：
4.4
通讯作者：
Thomas F. Gajewski;S. Schell;Frank W. Fitch
中科院分区：
文献类型：
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作者：
Thomas F. Gajewski;S. Schell;Frank W. Fitch
我们最近报道，高浓度的抗CD3单抗可以抑制依赖IL-2的TH1的增殖，但不能抑制TH2克隆的增殖。对TH1克隆的选择性抑制作用提示，这两个辅助性T细胞亚群可能使用不同的TCR相关信号转导机制。在本研究中，我们证明这种差异并不是由于TH1和TH2克隆在TCR表达水平上的显著差异。抗CD3单抗抑制TH1增殖的最大作用依赖于钙离子，提示TH2克隆的TCR复合体结扎后，细胞内游离钙浓度([Ca~(2+)]i)可能不会显著升高。钙离子载体抑制IL-2依赖的两个亚群的增殖，提示刺激升高的[Ca~(2+)]i的受体/配体系统有望抑制增殖。虽然在TH1克隆中很容易检测到[Ca~(2+)]i升高和肌醇磷酸盐的产生，但通过TCR复合体刺激TH2克隆后，没有检测到这些第二信使。此外，TH1克隆产生的淋巴因子对霍乱毒素、8-溴腺苷3‘：5’-环一磷酸和环孢素A的抑制比TH2克隆产生的淋巴因子更敏感。总之，这些结果表明，TH1和TH2克隆利用不同的TCR相关信号转导机制来表达淋巴因子基因。信号机制的差异表明，在体内发生TH1或TH2细胞不适当激活的情况下，有一个潜在的药物靶点进行干预。
We have reported recently that high concentrations of anti-CD3 mAb inhibited IL-2-dependent proliferation of TH1 but not TH2 clones. The selective inhibitory effect on TH1 clones suggested that the two helper T lymphocyte subsets might utilize different TCR-associated signal transduction mechanisms. In the present study, we demonstrate that this distinction was not due to a gross difference in the level of TCR expression by TH1 and TH2 clones. Inhibition of TH1 proliferation by anti-CD3 mAb appeared to depend on calcium for maximal effect, suggesting that a substantial elevation of intracellular free calcium concentration ([Ca2+]i) might not occur after ligation of the TCR complex of TH2 clones. Calcium ionophore inhibited IL-2-dependent proliferation of both subsets, suggesting that receptor/ligand systems which stimulate elevated [Ca2+]i would be expected to inhibit proliferation. Although elevated [Ca2+]i and generation of inositol phosphates were readily detected in TH1 clones, these second messengers were not detected following stimulation of TH2 clones via the TCR complex. In addition, lymphokine production by TH1 clones was more sensitive to inhibition by cholera toxin, 8-bromoadenosine 3':5'-cyclic monophosphate, and cyclosporin A than was lymphokine production by TH2 clones. Collectively, these results suggest that TH1 and TH2 clones utilize distinct TCR-associated signal transduction mechanisms for lymphokine gene expression. The difference in signaling mechanisms suggests a potential pharmacologic target for intervention in situations where inappropriate activation of TH1 or TH2 cells occurs in vivo.