Mannering S I, Zhan Y, Gilbertson B, Lieschke G J, Cheers C
Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia.
Immunology. 2000 Sep;101(1):132-9. doi: 10.1046/j.1365-2567.2000.00075.x.
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.
关于粒细胞集落刺激因子（G-CSF）在慢性细菌感染反应中的作用，目前所知甚少。为了解决这个问题，我们用鸟分枝杆菌感染了G-CSF基因敲除（G-CSF-/-）小鼠。尽管G-CSF-/-小鼠的骨髓细胞总数、集落形成造血细胞、粒细胞和骨髓单核细胞前体均有缺陷，但感染并未加剧。与野生型（WT）细胞相比，G-CSF-/-小鼠的腹腔细胞在体外与抗原培养时产生的一氧化氮（NO）较少。出乎意料的是，感染的G-CSF-/-小鼠的T细胞比野生型（WT）对照能够产生显著更多的干扰素-γ（IFN-γ）。即使在体外NO产生受到抑制时，G-CSF-/-小鼠的T细胞仍能产生更多的IFN-γ，而酶联免疫斑点分析（ELISPOT）显示G-CSF-/-小鼠中产生IFN-γ的细胞更多。这通过细胞内细胞因子染色（ICCS）得到证实，ICCS显示在鸟分枝杆菌感染后，G-CSF-/-小鼠体内产生IFN-γ的T细胞比WT对照更多。体内NO的缺乏可能使T细胞形成更高的产生IFN-γ的表型。因此，我们在这个慢性细菌感染模型中展示了G-CSF与T细胞产生IFN-γ之间的一种新关系。
