T lymphocytes from granulocyte colony-stimulating factor-/- mice produce large quantities of interferon-gamma in a chronic infection model.
Little is known about the role of granulocyte colony-stimulating factor (G-CSF) in the response to chronic bacterial infections. To address this we infected G-CSF knock out (G-CSF-/-) mice with Mycobacterium avium. Infection was not exacerbated in G-CSF-/- mice despite a deficiency in the total bone marrow cells, colony-forming haemopoietic cells, granulocytes and monocyte precursors in the bone marrow. Peritoneal cells from G-CSF-/- produced less nitric oxide (NO) upon culture in vitro with antigen than did wild-type (WT) cells. Unexpectedly, T cells from infected G-CSF-/- mice were able to produce significantly more interferon-gamma (IFN-gamma) than the wild type (WT) controls. T cells from G-CSF-/- mice still produced more IFN-gamma even when in vitro NO production was inhibited, while enzyme-linked immunospot assay (ELISPOT) assays showed more IFN-gamma-producing cells in the G-CSF-/- mice. This was confirmed by intracellular cytokine staining (ICCS), which showed that there were more IFN-gamma producing T cells in vivo in the G-CSF-/- than the WT controls following M. avium infection. It is possible that a deficit of NO in vivo allows T cells to develop a higher IFN-gamma-producing phenotype. Thus we show a novel relationship between G-CSF and IFN-gamma production by T cells revealed in this chronic bacterial infection model.
Mannering
S I
SI
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Zhan
Y
Y
Gilbertson
B
B
Lieschke
G J
GJ
Cheers
C
C
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D018929:Cell Culture Techniques; D002908:Chronic Disease; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009162:Mycobacterium avium; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D007371:Interferon-gamma