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.
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 gamma (IFN-gamma) 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.
Stephens
Robin
R
National Institute of Medical Research, The Ridgeway, Mill Hill London, NW7 1AA, United Kingdom.
Albano
Frank R
FR
Quin
Stuart
S
Pascal
Benjamin J
BJ
Harrison
Vicky
V
Stockinger
Brigitta
B
Kioussis
Dimitris
D
Weltzien
Hans-Ulrich
HU
Langhorne
Jean
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D016788:Plasmodium chabaudi / Q000276:immunology
D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1