Morrison W J, Young K, Offner H, Vandenbark A A
Neuroimmunology Research Laboratory, Veterans Administration Medical Center, Portland, OR 97207.
Cell Mol Biol Res. 1993;39(2):159-65.
Ganglioside (GM1) modulation of CD4 off the surface of T lymphocytes defined functions of the CD4 molecule during signal transduction through the T cell receptor (TCR)/CD3 complex. Antibody cross-linking of CD3 alone (3 x 3) stimulated phospholipase C (PLC) activity, rapid Ca2+ flux, and protein phosphorylations in freshly isolated human T lymphocytes. Antibody cross-linking of CD4 and CD3 (3 x 4) stimulated greater signaling than that caused by 3 x 3. Cross-linking CD4 alone did not stimulate these signaling processes. GM1-modulation of CD4 from the cell surface blocked all aspects of the augmented signaling imparted by CD4 co-modulation with CD3. In comparison, pretreatment with the protein tyrosine kinase inhibitor genistein inhibited 3 x 4-stimulated PLC activity and protein phosphorylation but not Ca2+ flux. Antibody cross-linking of the tyrosine phosphatase CD45 with 3 x 4 (3 x 4 x 45) also inhibited CD4-augmented phosphorylations and like genistein did not reduce Ca2+ levels. In conclusion, these data demonstrate that CD4 can augment signal transduction through the TCR/CD3 complex by its physical proximity to CD3. TCR/CD3-signaling augmentation by CD4 stimulated protein tyrosine kinases and PLC activities but stimulated intracellular Ca2+ flux through an independent mechanism(s).
神经节苷脂（GM1）对T淋巴细胞表面CD4的调节作用确定了CD4分子在通过T细胞受体（TCR）/CD3复合物进行信号转导过程中的功能。单独对CD3进行抗体交联（3×3）可刺激新鲜分离的人T淋巴细胞中的磷脂酶C（PLC）活性、快速的Ca2+通量和蛋白质磷酸化。对CD4和CD3进行抗体交联（3×4）所刺激的信号传导比3×3所引起的更强。单独交联CD4不会刺激这些信号传导过程。GM1对细胞表面CD4的调节作用阻断了由CD4与CD3共同调节所赋予的增强信号传导的各个方面。相比之下，用蛋白酪氨酸激酶抑制剂染料木黄酮预处理可抑制3×4刺激的PLC活性和蛋白质磷酸化，但不影响Ca2+通量。用3×4（3×4×45）对酪氨酸磷酸酶CD45进行抗体交联也可抑制CD4增强的磷酸化，并且与染料木黄酮一样不会降低Ca2+水平。总之，这些数据表明，CD4可通过与CD3的物理接近来增强通过TCR/CD3复合物的信号转导。CD4对TCR/CD3信号传导的增强作用刺激了蛋白酪氨酸激酶和PLC活性，但通过独立的机制刺激了细胞内Ca2+通量。
