Parasite antigen-driven basophils are a major source of IL-4 in human filarial infections
Parasite antigen-driven basophils are a major source of IL-4 in human filarial infections
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DOI：
10.4049/jimmunol.172.4.2439
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发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Nutman, TB
中科院分区：
文献类型：
--
作者：
Mitre, E;Taylor, RT;Nutman, TB
使用来自20例活动性丝虫病患者和9例未感染受试者的PBMC评估嗜碱性粒细胞对丝虫病感染中IL-4池的贡献。患者嗜碱性细胞释放组胺响应马来布鲁吉菌Ag （BmAg）。通过细胞内细胞因子流式细胞术评估，它们也在暴露于BmAg后2小时内释放IL-4。这种IL-4诱导是Ag特异性的，因为从未感染的受试者获得的暴露于bmag的嗜碱性粒细胞中未检测到IL-4。虽然丝虫病感染患者外周血中CD4(+) T细胞平均比嗜碱性细胞多64倍，但每100,000 PBMC中产生IL-4的嗜碱性细胞和CD4(+) T细胞的绝对数量是相等的（几何平均值：16个产生IL-4的嗜碱性细胞/100,000 PBMC vs 22个产生IL-4的CD4(+) T细胞/100,000 PBMC）。在低浓度和高浓度BmAg的作用下，嗜碱性细胞也会释放IL-4，而CD4(+) T细胞只有在高浓度BmAg的作用下才会释放IL-4，这就提高了嗜碱性细胞在体内释放IL-4的频率可能高于CD4(+) T细胞的可能性，因为它们的激活门槛较低。此外，ag刺激纯化的嗜碱性细胞或CD4(+) T细胞在体外产生IL-4的实验证明，在BmAg的作用下，嗜碱性细胞比CD4(+) T细胞释放更多的IL-4。这些结果表明，当丝虫病感染个体中存在Ag特异性IgE时，嗜碱性细胞通过释放IL-4来放大正在进行的Th2反应，其数量和频率可能高于CD4(+) T细胞。免疫学杂志，2004,32(2):2439-2445。
Basophil contribution to the IL-4 pool in filarial infections was assessed using PBMC from 20 patients with active filarial infections and from 9 uninfected subjects. Patient basophils released histamine in response to Brugia malayi Ag (BmAg). They also released IL-4 within 2 h after exposure to BmAg, as assessed by intracellular cytokine flow cytometry. This IL-4 induction was Ag specific, as IL-4 was not detected in BmAg-exposed basophils obtained from uninfected subjects. Although there were, on average, 64 times more CD4(+) T cells than basophils in the peripheral circulation of filaria-infected patients, the absolute numbers of basophils and CD4(+) T cells producing IL-4 per 100,000 PBMC were equivalent (geometric mean: 16 IL-4-producing basophils/100,000 PBMC vs 22 IL-4-producing CD4(+) T cells/100,000 PBMC). Basophils also released IL-4 in response to both low and high concentrations of BmAg, whereas CD4(+) T cells released IL-4 only after incubation with a high concentration of BmAg, raising the possibility that basophils, due to their lower threshold for activation, may actually release IL-4 more frequently than CD4(+) T cells in vivo. Furthermore, IL-4 production in vitro by Ag-stimulated purified basophils or CD4(+) T cells provided evidence that basophils release greater quantities of IL-4 per cell than CD4(+) T cells in response to BmAg. These results suggest that, when Ag-specific IgE is present in a filaria-infected individual, basophils function to amplify the ongoing Th2 response by releasing IL-4 in greater amounts and possibly more frequently than CD4(+) T cells in response to filarial Ag. The Journal of Immunology, 2004, 172: 2439-2445.