An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major
An immunomodulatory function for neutrophils during the induction of a CD4+ Th2 response in BALB/c mice infected with Leishmania major
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DOI：
10.4049/jimmunol.165.5.2628
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Louis, JA
中科院分区：
文献类型：
--
作者：
Tacchini-Cottier, F;Zweifel, C;Louis, JA
本文通过观察巨利什曼原虫（Leishmania major）感染小鼠后早期中性粒细胞（PMN）的短暂耗竭，探讨了PMN对小鼠CD_4（+）T淋巴细胞分化的可能免疫调节作用。在感染L. major阻止了IL-4 mRNA转录的早期爆发，否则会发生在易感BALB/c小鼠的引流淋巴结中。由于IL-4 mRNA转录物的这种早期爆发先前已显示指导来自该品系的小鼠中的Th 2分化，因此我们检测了感染后稍后时间点的PMN耗竭对Th亚群分化的影响。严重感染Th 2应答的降低与L.少校此外，在L.与接受对照抗体的感染的BALB/c小鼠不同，当在感染后24小时注射NIMP-R14 mAb时，PMN耗竭没有影响。中性粒细胞耗竭的保护作用是IL-12依赖性的，因为IL-12的中和作用逆转了中性粒细胞耗竭的保护作用。这些结果表明，中性粒细胞的早期波在对L.少校
The possible immunomodulatory role of polymorphonuclear leukocytes (PMN) in CD4(+) T lymphocyte differentiation in mice was examined by studying the effect of transient depletion of PMN during the early phase after Leishmania major delivery. A single injection of the PMN-depleting NIMP-R14 mAb 6 h before infection with L. major prevented the early burst of IL-4 mRNA transcription otherwise occurring in the draining lymph node of susceptible BALB/c mice. Since this early burst of IL-4 mRNA transcripts had previously been shown to instruct Th2 differentiation in mice from this strain, we examined the effect of PMN depletion on Th subset differentiation at later time points after infection, The transient depletion of PR IN in BALB/c mice was sufficient to inhibit Th2 cell development otherwise occurring after L. major infection. Decreased Th2 responses were paralleled with partial resolution of the footpad lesions induced by L. major. Furthermore, draining lymph node-derived CD4(+) T cells from PMN-depleted mice remained responsive to IL-12 after L. major infection, unlike those of infected BALB/c mice receiving control Ab, PMN depletion had no effect when the NIMP-R14 mAb was injected 24 h postinfection. The protective effect of PMN depletion was shown to be IL-12 dependent, as concomitant neutralization of IL-12 reversed the protective effect of PMN depletion, These results suggest a role for an early wave of PMN in the development of the Th2 response characteristic of mice susceptible to infection with L. major.