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Updated: May 28, 2026
Isolation and Analysis of Brain-sequestered Leukocytes from Plasmodium berghei ANKA-infected Mice
Published on: January 2, 2013
Blood-stage Plasmodium berghei infection generates a potent, specific CD8+ T-cell response despite residence largely
Lei Shong Lau1, Daniel Fernandez Ruiz, Gayle M Davey
1Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
Abstract:
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-γ and tumor necrosis factor-α. 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.
Insights
A strong CD8(+) T cell response, similar to viral immunity, targets malaria parasites during infection. These cytotoxic T lymphocytes (CTL) are crucial for fighting Plasmodium berghei ANKA, even when parasites are in red blood cells.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Murine cerebral malaria, caused by Plasmodium berghei ANKA, involves CD8(+) T cells as key disease effectors.
- Previous studies using model antigens showed cytotoxic T lymphocyte (CTL) induction, but direct evidence for responses to authentic parasite antigens was lacking.
Purpose of the Study:
- To investigate the magnitude and characteristics of the primary CD8(+) T cell response to authentic blood-stage Plasmodium berghei ANKA antigens.
- To determine if CTLs can be effectively induced against pathogens residing within red blood cells.
Main Methods:
- Flow cytometry to quantify parasite-specific CD8(+) T cells and assess cytokine production (IFN-γ, TNF-α).
- Analysis of granzyme B expression and cytolytic activity of CD8(+) T cells.
- Identification of major histocompatibility complex (MHC) class I-restricted epitopes recognized by CTLs.
Main Results:
- A robust, primary parasite-specific CTL response was observed, comprising up to 30% of splenic CD8(+) T cells.
- A significant proportion of these CTLs produced interferon-γ and tumor necrosis factor-α.
- The identified CTLs were cytolytic, expressed granzyme B, and recognized multiple MHC class I-restricted epitopes from authentic parasite antigens.
Conclusions:
- Plasmodium berghei ANKA infection induces a vigorous CTL response comparable to viral immunity.
- Effective CTL responses can be generated against pathogens sequestered within red blood cells, despite their lack of MHC class I antigen processing machinery.
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