A novel role for neutrophils as a source of T cell-recruiting chemokines IP-10 and Mig during the DTH response to HSV-1 antigen
A novel role for neutrophils as a source of T cell-recruiting chemokines IP-10 and Mig during the DTH response to HSV-1 antigen
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DOI：
10.1189/jlb.0904485
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发表时间：
2005-04-01
影响因子：
5.5
通讯作者：
Lausch, RN
中科院分区：
文献类型：
--
作者：
Molesworth-Kenyon, SJ;Oakes, JE;Lausch, RN
与CD 4（+）T细胞类似，中性粒细胞是对单纯疱疹病毒I型抗原的迟发型超敏反应（DTH）的重要参与者。然而，它们在这种细胞免疫反应中发挥的作用尚不清楚。最近认识到中性粒细胞是趋化因子的有效生产者，这使我们假设它们可能有助于招募CD 4+效应T细胞。在本研究中，我们发现中性粒细胞耗竭伴随着迁移到DTH位点的表达CD 4（+）和CXC受体3（+）（CXCR 3（+））的细胞数量的显著减少以及IFN-γ（Mig）诱导的干扰素诱导蛋白10（IP-10）和单核因子水平的急剧下降。用IFN-γ直接刺激纯化的小鼠嗜中性粒细胞分泌这些趋化因子，DTH位点的嗜中性粒细胞表达IP-10。IFN-γ敲除小鼠在DTH攻击后表现出抑制性耳肿胀，产生很少的IP-10，没有Mig。用IFN-γ重建这些小鼠诱导CXCR 3配体合成。中性粒细胞或CD 4（+）T细胞的耗竭而非CD 8（+）T细胞的耗竭显著降低IFN-γ水平，表明前者是该细胞因子的直接（或间接）细胞来源。总的来说，我们的研究结果支持这一假设，即中性粒细胞产生的T细胞募集趋化因子有助于调节和放大的DTH反应。
Analogous to CD4(+) T cells, neutrophils are essential participants in delayed-type hypersensitivity (DTH) to Herpes simplex virus type I antigen. However, what role they play in this cellular immune response is unclear. The recent recognition that neutrophils are potent producers of chemokines led us to hypothesize that they may help recruit CD4+ effector T cells. In the present study, we show that neutrophil depletion was accompanied by a marked decrease in the numbers of CD4(+) and CXC receptor 3(+) (CXCR3(+))-expressing cells migrating to the DTH site and a sharp drop in the levels of interferon-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig). Purified mouse neutrophils were stimulated directly by IFN-gamma to secrete these chemokines, and neutrophils at the DTH site expressed IP-10. IFN-gamma knockout mice, which manifested depressed ear-swelling following DTH challenge, made little IP-10 and no Mig. Reconstitution of these mice with IFN-gamma induced CXCR3 ligand synthesis. Depletion of neutrophils or CD4(+) T cells but not CD8(+) T cells markedly reduced IFN-gamma levels, suggesting the former were direct (or indirect) cellular sources of this cytokine. Collectively, our results support the hypothesis that neutrophil production of T cell-recruiting chemokines contributes to the regulation and amplification of the DTH response.