Modulation of CD1d-restricted NKT cell responses by CD4
Modulation of CD1d-restricted NKT cell responses by CD4
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DOI：
10.1189/jlb.0307163
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发表时间：
2007-12-01
影响因子：
5.5
通讯作者：
Gumperz, Jenny E.
中科院分区：
文献类型：
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作者：
Chen, Xiuxu;Wang, Xiaohua;Gumperz, Jenny E.
CD4（+）和CD4(-) NKT细胞群在功能上是不同的，但CD4分子在NKT细胞活化中的作用尚不清楚。在这里，我们使用人类cd1限制的NKT细胞克隆来研究CD4对NKT细胞功能反应的贡献。CD4与TCR/CD3复合物结合导致CD4(+) NKT细胞克隆细胞因子分泌增强，钙通量增加，表明CD4在这些细胞中具有功能活性。CD4阻断特异性抑制CD1d(+) APCs对CD4(+) NKT细胞克隆的细胞因子分泌和增殖，但不影响细胞毒性，表明CD4优先调节一些NKT细胞的功能反应，而不是其他功能反应。抗CD4单抗治疗抑制了NKT细胞对MHC II+类和MHC II+类apc的反应，表明其作用不是由于阻断CD4与apc II类分子的结合。抗cd4单抗的抑制作用也不需要NKT细胞识别CD1d，因为钙通量在抗cd3单抗刺激下减少。Western blot分析显示，抗cd4治疗导致p56（lck）抑制位点（酪氨酸505）磷酸化增加。因此，CD4阻断干扰了NKT细胞中cd3介导的信号事件的过程。这些结果表明，CD4可以独立于apc上CD4配体的存在而促进NKT细胞活化，并表明它优先调节细胞因子和增殖反应。
CD4(+) and CD4(-) NKT cell populations have been shown to be functionally distinct, but the role of CD4 molecules in NKT cell activation is not clear. Here, we have used human CD1d-restricted NKT cell clones to investigate the contribution of CD4 to NKT cell functional responses. Coligation of CD4 with the TCR/CD3 complex resulted in enhanced cytokine secretion and increased calcium flux by CD4(+) NKT cell clones, indicating that CD4 is functionally active in these cells. CD4 blockade specifically inhibited cytokine secretion and proliferation of CD4(+) NKT cell clones in response to CD1d(+) APCs but did not affect cytotoxicity, suggesting that CD4 preferentially modulates some NKT cell functional responses and not others. Anti-CD4 mAb treatment inhibited NKT cell responses to both MHC class II+ and MHC class II+ APCs, indicating that its effect was not due to blocking CD4 binding to MHC class II molecules on APCs. The inhibitory effect of the anti-CD4 mAb also did not require recognition of CD1d by the NKT cell, since calcium flux was reduced in response to anti-CD3 mAb stimulation. Western blot analysis revealed that anti-CD4 treatment resulted in increased phosphorylation of an inhibitory site of p56(lck) ( tyrosine 505). Thus, CD4 blockade interferes with the course of CD3-mediated signaling events in NKT cells. These results indicate that CD4 can contribute to NKT cell activation independently of the presence of a CD4-ligand on APCs and suggest that it preferentially modulates cytokine and proliferative responses.