Malaria-specific and nonspecific activation of CD8+ T cells during blood stage of Plasmodium berghei infection.
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.
Miyakoda
Mana
M
Department of Molecular Microbiology and Immunology, Division of Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Kimura
Daisuke
D
Yuda
Masao
M
Chinzei
Yasuo
Y
Shibata
Yoshisada
Y
Honma
Kiri
K
Yui
Katsuyuki
K
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D016779:Malaria, Cerebral / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D018512:Parasitemia; D010962:Plasmodium berghei / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D010047:Ovalbumin