Malaria-specific and nonspecific activation of CD8+ T cells during blood stage of Plasmodium berghei infection.

Abstract

Cerebral malaria is one of the severe complications of Plasmodium falciparum infection. Studies using a rodent model of Plasmodium berghei ANKA infection established that CD8(+) T cells are involved in the pathogenesis of cerebral malaria. However, it is unclear whether and how Plasmodium-specific CD8(+) T cells can be activated during the erythrocyte stage of malaria infection. We generated recombinant Plasmodium berghei ANKA expressing OVA (OVA-PbA) to investigate the parasite-specific T cell responses during malaria infection. Using this model system, we demonstrate two types of CD8(+) T cell activations during the infection with malaria parasite. Ag (OVA)-specific CD8(+) T cells were activated by TAP-dependent cross-presentation during infection with OVA-PbA leading to their expression of an activation phenotype and granzyme B and the development to functional CTL. These highly activated CD8(+) T cells were preferentially sequestered in the brain, although it was unclear whether these cells were involved in the pathogenesis of cerebral malaria. Activation of OVA-specific CD8(+) T cells in RAG2 knockout TCR-transgenic mice during infection with OVA-PbA did not have a protective role but rather was pathogenic to the host as shown by their higher parasitemia and earlier death when compared with RAG2 knockout mice. The OVA-specific CD8(+) T cells, however, were also activated during infection with wild-type parasites in an Ag-nonspecific manner, although the levels of activation were much lower. This nonspecific activation occurred in a TAP-independent manner, appeared to require NK cells, and was not by itself pathogenic to the host.

• Authors: Mana Miyakoda, Daisuke Kimura, Masao Yuda, Yasuo Chinzei, Yoshisada Shibata, Kiri Honma, Katsuyuki Yui
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 2 Pg. 1420-8 (Jul 15 2008) ISSN: 1550-6606 [Electronic] United States
• PMID: 18606696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• Interferon-gamma
• Ovalbumin

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cross-Priming
• Interferon-gamma (blood, immunology, metabolism)
• Killer Cells, Natural (immunology)
• Lymphocyte Activation
• Malaria (immunology)
• Malaria, Cerebral (blood, immunology, parasitology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Ovalbumin (immunology)
• Parasitemia
• Plasmodium berghei (immunology)
• Recombinant Fusion Proteins (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (immunology)