Differential CC chemokine-induced enhancement of T helper cell cytokine production.
Differential CC chemokine-induced enhancement of T helper cell cytokine production.
复制标题
DOI：
10.4049/jimmunol.158.9.4129
复制
发表时间：
1997-05
影响因子：
4.4
通讯作者：
W. Karpus;N. Lukacs;K. J. Kennedy;W. S. Smith;S. Hurst;T. Barrett
中科院分区：
文献类型：
--
作者：
W. Karpus;N. Lukacs;K. J. Kennedy;W. S. Smith;S. Hurst;T. Barrett
趋化因子是一个小分子量的家族。诱导白细胞趋化和趋化作用的细胞因子。这些分子是七次跨膜、Gi 蛋白连接受体的配体，除了参与白细胞的跨内皮迁移外，还可诱导人 T 细胞中的信号级联反应，并为 T 细胞激活提供共刺激。为了解决趋化因子在调节 Th 细胞细胞因子产生中的作用，我们利用了 OVA 特异性 TCR 转基因 (Tg+) 模型。通过 TCR 刺激并在巨噬细胞炎症蛋白 1α (MIP-1α) 存在下孵育的细胞显示出 IFN-γ 产生增强，而在单核细胞趋化蛋白 1 (MCP-1) 存在下孵育的细胞显示出 IL-4 产生增强。无论用抗 CD3 mAb 还是 OVA 肽刺激 TCR Tg+ T 细胞，都获得了类似的结果。在存在趋化因子的情况下对 T 细胞进行初次刺激，然后单独使用抗 TCR 克隆型单克隆抗体（无外源趋化因子）进行二次刺激和三次刺激，结果表明 MIP-1α 刺激的 IFN-γ 产生增强，MCP-1 刺激的 IL-4 产生增强。从 Tg+ 小鼠与 RAG-1 缺陷型小鼠杂交获得的初始 Tg+ T 细胞，与 MIP-1α 孵育时显示出 IFN-γ 生成增强，与 MCP-1 孵育时显示出 IL-4 生成增强。这些结果表明，CC 趋化因子除了调节白细胞运输外，还在调节初始 Th 细胞细胞因子的产生中发挥作用。
Chemokines are a family of small m.w. cytokines that induce chemotaxis and chemokinesis of leukocytes. These molecules are ligands for seven-transmembrane, Gi protein-linked receptors that induce a signaling cascade in human T cells and provide costimulation for T cell activation, in addition to participating in transendothelial migration of leukocytes. To address the role of chemokines in the regulation of Th cell cytokine production, we utilized an OVA-specific TCR transgenic (Tg+) model. Cells stimulated through the TCR and incubated in the presence of macrophage inflammatory protein-1alpha (MIP-1alpha) showed enhanced IFN-gamma production, whereas cells incubated in the presence of monocyte chemotactic protein-1 (MCP-1) showed enhanced IL-4 production. Similar results were obtained whether TCR Tg+ T cells were stimulated with anti-CD3 mAb or OVA peptide. Primary stimulation of T cells in the presence of chemokines, followed by secondary stimulation and tertiary stimulation with anti-TCR clonotype mAb alone (no exogenous chemokines), revealed an enhanced IFN-gamma production for MIP-1alpha stimulation and IL-4 production for MCP-1 stimulation. Naive Tg+ T cells, obtained from Tg+ mice crossed to RAG-1-deficient mice, showed enhanced IFN-gamma production when incubated with MIP-1alpha and enhanced IL-4 production when incubated with MCP-1. These results suggest CC chemokines play a role in regulating naive Th cell cytokine production, in addition to regulating leukocyte trafficking.