Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated immune response.
Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated immune response.
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DOI：
10.4049/jimmunol.162.8.4824
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发表时间：
1999-04
影响因子：
4.4
通讯作者：
H. Doyle;J. Murphy
中科院分区：
文献类型：
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作者：
H. Doyle;J. Murphy
在细胞介导免疫（CMI）反应中，活化的T淋巴细胞在协调细胞浸润中起关键作用。TCA3是一种C-C趋化因子，由ag活化的T细胞产生，对小鼠CMI反应中的两种细胞类型中性粒细胞和巨噬细胞具有趋化作用。使用明胶海绵模型延迟型超敏反应（DTH），我们发现TCA3是小鼠抗隐球菌CMI反应表达阶段的一个组成部分。TCA3 mRNA水平在抗隐球菌DTH反应中升高，同时观察到中性粒细胞和淋巴细胞的峰值流入。免疫小鼠中TCA3的中和导致DTH反应部位的中性粒细胞和淋巴细胞数量减少。然而，当将rTCA3注射到幼稚小鼠的海绵中时，海绵中只吸引中性粒细胞，这表明TCA3对中性粒细胞具有趋化作用，而对淋巴细胞没有趋化作用。我们发现TCA3通过影响至少一种其他趋化淋巴细胞的趋化因子，间接地将淋巴细胞吸引到dth反应海绵中。在评估的两种吸引淋巴细胞的趋化因子，单核细胞趋化蛋白-1和巨噬细胞炎症蛋白-1 α (mip -1 α)中，当TCA3被中和时，只有mip -1 α降低，表明TCA3影响mip -1 α的水平，而mip -1 α将淋巴细胞吸引到海绵中。TCA3在感染小鼠的肺和脑中也起着保护新生隐球菌的作用，TCA3的中和可导致这两个器官中新生隐球菌CFU的增加。
Activated T lymphocytes play a crucial role in orchestrating cellular infiltration during a cell-mediated immune (CMI) reaction. TCA3, a C-C chemokine, is produced by Ag-activated T cells and is chemotactic for neutrophils and macrophages, two cell types in a murine CMI reaction. Using a gelatin sponge model for delayed-type hypersensitivity (DTH), we show that TCA3 is a component of the expression phase of an anticryptococcal CMI response in mice. TCA3 mRNA levels are augmented in anticryptococcal DTH reactions at the same time peak influxes of neutrophils and lymphocytes are observed. Neutralization of TCA3 in immunized mice results in reduced numbers of neutrophils and lymphocytes at DTH reaction sites. However, when rTCA3 is injected into sponges in naive mice, only neutrophils are attracted into the sponges, indicating TCA3 is chemotactic for neutrophils, but not lymphocytes. We show that TCA3 is indirectly attracting lymphocytes into DTH-reactive sponges by affecting at least one other chemokine that is chemotactic for lymphocytes. Of the two lymphocyte-attracting chemokines assessed, monocyte-chemotactic protein-1 and macrophage-inflammatory protein-1alpha (MIP-1alpha), only MIP-1alpha was reduced when TCA3 was neutralized, indicating that TCA3 affects the levels of MIP-1alpha, which attracts lymphocytes into the sponges. TCA3 also plays a role in protection against Cryptococcus neoformans in the lungs and brains of infected mice, as evidenced by the fact that neutralization of TCA3 results in increased C. neoformans CFU in those two organs.