@article{oai:nagasaki-u.repo.nii.ac.jp:00006911,
 author = {Kimura, Kazumi and Kimura, Daisuke and Matsushima, Yoshifumi and Miyakoda, Mana and Honma, Kiri and Yuda, Masao and Yui, Katsuyuki},
 issue = {10},
 journal = {Infection and Immunity},
 month = {Oct},
 note = {Following Anopheles mosquito-mediated introduction into a human host, Plasmodium parasites infect hepatocytes and undergo intensive replication. Accumulating evidence indicates that CD8+ T cells induced by immunization with attenuated Plasmodium sporozoites can confer sterile immunity at the liver stage of infection; however, the mechanisms underlying this protection are not clearly understood. To address this, we generated recombinant Plasmodium berghei ANKA expressing a fusion protein of an ovalbumin epitope and green fluorescent protein in the cytoplasm of the parasite. We have shown that the ovalbumin epitope is presented by infected liver cells in a manner dependent on a transporter associated with antigen processing and becomes a target of specific CD8+ T cells from the T cell receptor transgenic mouse line OT-I, leading to protection at the liver stage of Plasmodium infection. We visualized the interaction between OT-I cells and infected hepatocytes by intravital imaging using two-photon microscopy. OT-I cells formed clusters around infected hepatocytes, leading to the elimination of the intrahepatic parasites and subsequent formation of large clusters of OT-I cells in the liver. Gamma interferon expressed in CD8+ T cells was dispensable for this protective response. Additionally, we found that polyclonal ovalbumin-specific memory CD8+ T cells induced by de novo immunization were able to confer sterile protection, although the threshold frequency of the protection was relatively high. These studies revealed a novel mechanism of specific CD8+ T cell-mediated protective immunity and demonstrated that proteins expressed in the cytoplasm of Plasmodium parasites can become targets of specific CD8+ T cells during liver-stage infection., Infection and Immunity, 81(10), pp.3825-3834; 2013},
 pages = {3825--3834},
 title = {CD8+ T Cells Specific for a Malaria Cytoplasmic Antigen Form Clusters around Infected Hepatocytes and Are Protective at the Liver Stage of Infection},
 volume = {81},
 year = {2013}
}