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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1676-1684.
Prepublished online as a Blood First Edition Paper on May 12, 2005; DOI 10.1182/blood-2004-10-4047.
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IMMUNOBIOLOGY
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, and
Jean Langhorne
From the Division of Parasitology, National Institute of Medical Research, The Ridgeway, Mill Hill, London, United Kingdom; Division of Molecular Immunology, National Institute of Medical Research, The Ridgeway, Mill Hill, London, United Kingdom; and Max Planck Institute for Immunobiology, Freiburg, Germany.
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 (IFN- ) 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. (Blood. 2005;106:1676-1684)

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