T lymphocytes from granulocyte colony-stimulating factor(-/-) mice producelarge 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 in fected 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 les s 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 p roduce 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-C SF-/- than the WT controls following M. avium infection. It is possible tha t a deficit of NO in vivo allows T cells to develop a higher IFN-gamma-prod ucing phenotype. Thus we show a novel relationship between G-CSF and IFN-ga mma production by T cells revealed in this chronic bacterial infection mode l.