Metcalfe S, Alexander D, Turner J
Department of Surgery, University of Cambridge, United Kingdom.
Cell Immunol. 1994 Oct 1;158(1):46-58. doi: 10.1006/cimm.1994.1255.
Antigen-specific signal transduction leading to IL2 induction and secretion in the T cell line 171 is augmented by association of p56lck with CD4. Although no change in cytoplasmic calcium level ([Ca2+]i) was detectable during antigen-specific signal transduction of 171-CD4+ cells, IL2 induction was inhibited by FK506 and CsA. Since these drugs are thought to act selectively by inhibiting calcineurin, a calcium-calmodulin-dependent protein phosphatase associated with activation of the IL2 promoter, we considered the possibility that calcineurin is constitutively active in 171 cells. However, we found no evidence for this because PMA failed to supplement any putatively active calcineurin to induce IL2 secretion. We suggest that IL2 secretion induced by antigen presentation to TCR/CD4/p56lck requires an FK506 and cyclosporin A-sensitive step which may be independent of calcium signaling. Rapamycin did not inhibit IL2 secretion induced by TCR/CD4/p56lck, emphasizing the specific action of FK506 and cyclosporin A.
在T细胞系171中，导致白细胞介素2（IL2）诱导和分泌的抗原特异性信号转导通过p56lck与CD4的结合而增强。尽管在171 - CD4 +细胞的抗原特异性信号转导过程中未检测到细胞质钙水平（[Ca2 +]i）的变化，但IL2的诱导受到FK506和环孢素A（CsA）的抑制。由于这些药物被认为通过抑制钙调磷酸酶而发挥选择性作用，钙调磷酸酶是一种与IL2启动子激活相关的钙 - 钙调蛋白依赖性蛋白磷酸酶，我们考虑了钙调磷酸酶在171细胞中组成性激活的可能性。然而，我们没有找到支持这一点的证据，因为佛波酯（PMA）未能补充任何假定具有活性的钙调磷酸酶来诱导IL2分泌。我们认为，抗原呈递给TCR / CD4 / p56lck所诱导的IL2分泌需要一个对FK506和环孢素A敏感的步骤，这一步骤可能独立于钙信号传导。雷帕霉素不抑制由TCR / CD4 / p56lck诱导的IL2分泌，强调了FK506和环孢素A的特异性作用。
