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

By R. Stephens, F. Albano, S. Quin, B. Pascal, V. Harrison, B. Stockinger, D. Kioussis, H. Weltzien and J. Langhorne


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<sup>+</sup> 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<sup>+</sup> 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

Year: 2005
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Provided by: MPG.PuRe
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