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Publication : 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.

First Author  Molesworth-Kenyon SJ Year  2005
Journal  J Leukoc Biol Volume  77
Issue  4 Pages  552-9
PubMed ID  15629884 Mgi Jnum  J:97440
Mgi Id  MGI:3575457 Doi  10.1189/jlb.0904485
Citation  Molesworth-Kenyon SJ, et al. (2005) 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. J Leukoc Biol 77(4):552-9
abstractText  Analogous to CD4(+) T cells, neutrophils are essential participants in delayed-type hypersensitivity (DTH) to Herpes simplex virus type 1 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.
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