The role of intrahepatic lymphocytes in mediating protective immunity induced by attenuated Plasmodium berghei sporozoites

Authors

  • Urszula Krzych,

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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  • Robert Schwenk,

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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  • Mimi Guebre-Xabier,

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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  • Peifang Sun,

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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  • Dupeh Palmer,

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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  • Katherine White,

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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  • Isaac Chalom

    1. Department of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Forest Glen Annex, Washington DC, USA
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Correspondence to:Urszula Krzych
Department of Immunology CD&I
Bldg 503 Forest Glen Annex
Walter Reed Army Institute of Research
Washington DC 20307-5100
USA
Fax: 1 301 319 9012
e-mail: Urszula.Krzych@na.AMEDD.army.mil

Abstract

Summary: Exposure to irradiated Plasmodium sporozoites (g-spz) results in protection against malaria. Like infectious spz, g-spz colonize hepatocytes to undergo maturation. Disruption of liver stage development prevents the generation of protection, which appears, therefore, to depend on liver stage antigens. Although some mechanisms of protection have been identified, they do not include a role for intrahepatic mononuclear cells (IHMC). We demonstrated that P. berghei g-spz-immune murine IHMC adoptively transfer protection to naive recipients. Characterization of intrahepatic CD4+ T cells revealed an immediate, albeit transient, response to g-spz, while the response of CD8+ T cells is delayed until acquisition of protection. It is presumed that activated CD8+ T cells home to the liver to die; g-spz-induced CD8+CD45RBloCD44hi T cells, however, persist in the liver, but not the spleen, during protracted protection. The association between CD8+CD45RBloCD44hi T cells and protection has been verified using MHC class I and CD1 knockout mice and mice with disrupted liver stage parasites. Based on kinetic studies, we propose that interferon-g, presumably released by intrahepatic effector CD8+ T cells, mediates protection; the persistence of CD8+ T cells is, in turn, linked to Plasmodium antigen depots and cytokines released by CD4+ T cells and/or NK T cells.

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