{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:33:41Z","timestamp":1791272021261,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:00:00Z","timestamp":1214870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.4049\/jimmunol.181.2.1420","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:27:05Z","timestamp":1397849225000},"page":"1420-1428","source":"Crossref","is-referenced-by-count":76,"title":["Malaria-Specific and Nonspecific Activation of CD8+ T Cells during Blood Stage of\n                    <i>Plasmodium berghei<\/i>\n                    Infection"],"prefix":"10.1093","volume":"181","author":[{"given":"Mana","family":"Miyakoda","sequence":"first","affiliation":[{"name":"Division of Immunology, Department of Molecular Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Molecular Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Yuda","sequence":"additional","affiliation":[{"name":"Department of Medical Zoology, School of Medicine, Mie University , Tsu,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Chinzei","sequence":"additional","affiliation":[{"name":"Department of Medical Zoology, School of Medicine, Mie University , Tsu,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshisada","family":"Shibata","sequence":"additional","affiliation":[{"name":"Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiri","family":"Honma","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Molecular Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Yui","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Molecular Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,7,15]]},"reference":[{"key":"2026012807101327000_R1","first-page":"3081","article-title":"Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi","volume-title":"Infect. 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