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Blood-Stage Plasmodium berghei Infection Generates a Potent, Specific CD8(+) T-Cell Response Despite Residence Largely in Cells Lacking MHC I Processing Machinery

  作者 Lau, LS; Ruiz, DF; Davey, GM; de Koning-Ward, TF; Papenfuss, AT; Carbone, FR; Brooks, AG; Crabb, BS; Heath, WR  
  选自 期刊  Journal of Infectious Diseases;  卷期  2011年204-12;  页码  1989-1996  
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[摘要]Murine cerebral malaria is a complex disease caused by Plasmodium berghei ANKA infection. Several cell types, including CD8(+) T cells, are essential effectors of disease. Although the use of transgenic parasites expressing model antigens has revealed the induction of cytotoxic T lymphocytes (CTL) specific for these model antigens, there is no direct evidence for a response to authentic blood-stage parasite antigens, nor any knowledge of its magnitude. Our studies show that there is a dramatic primary parasite-specific CTL response, akin to viral immunity, reaching approximately 30% of splenic CD8(+) T cells, with many producing interferon-gamma and tumor necrosis factor-alpha. These cells express granzyme B and other markers of specific responders, are cytolytic, and respond to a broad array of major histocompatibility complex (MHC) I-restricted epitopes, 5 of which are identified here. Our studies indicate that vigorous CTL responses can be induced to pathogens even when they largely reside in red blood cells, which lack MHC I processing machinery.

 
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