Theodore A C, Center D M, Nicoll J, Fine G, Kornfeld H, Cruikshank W W
The Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
J Immunol. 1996 Sep 1;157(5):1958-64.
CD4 participation in TCR/CD3-associated activation through interaction with the MHC class II Ags results in formation of a CD4-TCR/CD3 complex capable of maximal signal transduction. When CD4 binds to alternative ligands such as HIV-1 gp120 or anti-CD4 Abs, Ag stimulation of TCR/CD3 is markedly inhibited, and an unresponsive state develops. To determine if the natural CD4 ligand interleukin-16 also induces unresponsiveness, we tested the effects of rIL-16 on T cell proliferation in mixed lymphocyte reactions. rIL-16 suppressed T cell proliferation in a dose-dependent manner at concentrations of 10(-11) to 10(-7) M. Inhibition of proliferation was present on days 5 to 9 of the mixed lymphocyte reaction. rIL-16 did not modulate membrane CD4, significantly change basal [3H]thymidine incorporation in resting T lymphocytes, or alter viability. The suppressive effect was specifically blocked by preincubation with neutralizing anti-rIL-16 mAb or with recombinant soluble CD4. While the expression of IL-2R on responder cells was unaffected by rIL-16, the addition of exogenous rIL-2 did not restore T cell responsiveness. The unresponsiveness induced by rIL-16 is distinct from that of other CD4 ligands in that CD4 and IL-2R expression are unaffected. The failure of rIL-2 to restore proliferation suggests that the decrease in T cell responsiveness induced by rIL-16 may result from an interruption in the IL-2R-signaling mechanism. These results may help explain how CD4 delivers both activating and inhibitory signals and provides a rationale for the role of IL-16 in the regulation of immune responses.
CD4 通过与 MHC II 类抗原相互作用参与 TCR/CD3 相关的激活过程，导致形成能够进行最大信号转导的 CD4 - TCR/CD3 复合物。当 CD4 与诸如 HIV - 1 gp120 或抗 CD4 抗体等替代配体结合时，TCR/CD3 的抗原刺激会受到显著抑制，并产生无反应状态。为了确定天然 CD4 配体白细胞介素 - 16 是否也会诱导无反应状态，我们在混合淋巴细胞反应中测试了重组白细胞介素 - 16 对 T 细胞增殖的影响。重组白细胞介素 - 16 在浓度为 10(-11) 至 10(-7) M 时以剂量依赖方式抑制 T 细胞增殖。在混合淋巴细胞反应的第 5 至 9 天出现增殖抑制。重组白细胞介素 - 16 未调节膜 CD4，未显著改变静息 T 淋巴细胞中基础 [3H]胸苷掺入量，也未改变活力。通过用中和抗重组白细胞介素 - 16 单克隆抗体或重组可溶性 CD4 预孵育可特异性阻断抑制作用。虽然反应细胞上 IL - 2R 的表达不受重组白细胞介素 - 16 的影响，但添加外源性重组白细胞介素 - 2 并不能恢复 T 细胞反应性。重组白细胞介素 - 16 诱导的无反应状态与其他 CD4 配体不同，因为 CD4 和 IL - 2R 的表达不受影响。重组白细胞介素 - 2 未能恢复增殖表明重组白细胞介素 - 16 诱导的 T 细胞反应性降低可能是由于 IL - 2R 信号传导机制中断所致。这些结果可能有助于解释 CD4 如何传递激活和抑制信号，并为白细胞介素 - 16 在免疫反应调节中的作用提供理论依据。
