Malaria-specific transgenic CD4+ T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance

Robin Stephens, Frank R. Albano, Stuart Quin, Benjamin J. Pascal, Vicky Harrison, Brigitta Stockinger, Dimitris Kioussis, Hans Ulrich Weltzien, Jean Langhorne

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79 Scopus citations

Abstract

T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4+ T cells expand and produce interferon γ (IFN-γ) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4+ cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malaria-specific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine.

Original languageEnglish (US)
Pages (from-to)1676-1684
Number of pages9
JournalBlood
Volume106
Issue number5
DOIs
StatePublished - Sep 1 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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