Role of T cells in innate and adaptive immunity against murine Burkholderia pseudomallei infection

被引:96
|
作者
Haque, A
Easton, A
Smith, D
O'Garra, A
Van Rooijen, N
Lertmemongkolchai, G
Titball, RW
Bancroft, GJ
机构
[1] London Sch Hyg & Trop Med, Immunol Unit, Dept Infect & Trop Dis, London WC1E 7HT, England
[2] Natl Inst Med Res, London NW7 1AA, England
[3] Def Sci & Technol Lab, Salisbury, Wilts, England
[4] Vrije Univ Amsterdam, Dept Mol Cell Biol, Amsterdam, Netherlands
[5] Khon Kaen Univ, Dept Clin Immunol, Khon Kaen, Thailand
来源
JOURNAL OF INFECTIOUS DISEASES | 2006年 / 193卷 / 03期
基金
英国医学研究理事会;
关键词
D O I
10.1086/498983
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Antigen-specific T cells are important sources of interferon (IFN)-gamma for acquired immunity to intracellular pathogens, but they can also produce IFN-gamma directly via a "bystander" activation pathway in response to proinflammatory cytokines. We investigated the in vivo role of cytokine- versus antigen-mediated T cell activation in resistance to the pathogenic bacterium Burkholderia pseudomallei. IFN-gamma, interleukin (IL)-12, and IL-18 were essential for initial bacterial control in infected mice. B. pseudomallei infection rapidly generated a potent IFN-gamma response from natural killer (NK) cells, NK T cells, conventional T cells, and other cell types within 16 h after infection, in an IL-12- and IL-18-dependent manner. However, early T cell- and NK cell derived IFN-g responses were functionally redundant in cell depletion studies, with IFN-g produced by other cell types, such as major histocompatibility complex class IIint F4/80(+) macrophages being sufficient for initial resistance. In contrast, B. pseudomallei-specific CD4(+) T cells played an important role during the later stage of infection. Thus, the T cell response to primary B. pseudomallei infection is biphasic, an early cytokine-induced phase in which T cells appear to be functionally redundant for initial bacterial clearance, followed by a later antigen-induced phase in which B. pseudomallei-specific T cells, in particular CD4(+) T cells, are important for host resistance.
引用
收藏
页码:370 / 379
页数:10
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