Bystander Activation of CD8+ T Cells Contributes to the Rapid Production of IFN-γ in Response to Bacterial Pathogens
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- Ganjana Lertmemongkolchai
- *Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom;
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- Guifang Cai
- ‡School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
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- Christopher A. Hunter
- ‡School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
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- Gregory J. Bancroft
- *Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom;
説明
<jats:title>Abstract</jats:title> <jats:p>The bacterium Burkholderia pseudomallei causes a life-threatening disease called melioidosis. In vivo experiments in mice have identified that a rapid IFN-γ response is essential for host survival. To identify the cellular sources of IFN-γ, spleen cells from uninfected mice were stimulated with B. pseudomallei in vitro and assayed by ELISA and flow cytometry. Costaining for intracellular IFN-γ vs cell surface markers demonstrated that NK cells and, more surprisingly, CD8+ T cells were the dominant sources of IFN-γ. IFN-γ+ NK cells were detectable after 5 h and IFN-γ+ CD8+ T cells within 15 h after addition of bacteria. IFN-γ production by both cell populations was inhibited by coincubation with neutralizing mAb to IL-12 or IL-18, while a mAb to TNF had much less effect. Three-color flow cytometry showed that IFN-γ-producing CD8+ T cells were of the CD44high phenotype. The preferential activation of NK cells and CD8+ T cells, rather than CD4+ T cells, was also observed in response to Listeria monocytogenes or a combination of IL-12 and IL-18 both in vitro and in vivo. This rapid mechanism of CD8+ T cell activation may be an important component of innate immunity to intracellular pathogens.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 166 (2), 1097-1105, 2001-01-15
The American Association of Immunologists