CD8+ T Cells Specific for a Malaria Cytoplasmic Antigen Form Clusters around Infected Hepatocytes and Are Protective at the Liver Stage of Infection

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.;開始ページ : 3825;終了ページ : 3834;元資料の権利情報 : ©2013, American Society for Microbiology.

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書名 CD8+ T Cells Specific for a Malaria Cytoplasmic Antigen Form Clusters around Infected Hepatocytes and Are Protective at the Liver Stage of Infection
著作者等 American Society for Microbiology
木村 一美
書名別名 マラリア細胞質内抗原特異的 CD8+ T 細胞は、感染肝細胞周囲にクラスターを形成し肝細胞期で防御する
出版元 American Society for Microbiology
ページ数 v.
大きさ 26-28 cm
ISSN 00199567
NCID AA00673732
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言語 英語
出版国 アメリカ合衆国
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