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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
Author(s) -
MolesworthKenyon S. J.,
Oakes J. E.,
Lausch R. N.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0904485
Subject(s) - biology , chemokine , cxcr3 , immunology , monokine , cd8 , t cell , immune system , cytokine , antigen , cxc chemokine receptors , chemotaxis , chemokine receptor , microbiology and biotechnology , receptor , biochemistry
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‐γ (Mig). Purified mouse neutrophils were stimulated directly by IFN‐γ to secrete these chemokines, and neutrophils at the DTH site expressed IP‐10. IFN‐γ knockout mice, which manifested depressed ear‐swelling following DTH challenge, made little IP‐10 and no Mig. Reconstitution of these mice with IFN‐γ induced CXCR3 ligand synthesis. Depletion of neutrophils or CD4 + T cells but not CD8 + T cells markedly reduced IFN‐γ 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.