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

Blood. 2005 Sep 1;106(5):1676-84. doi: 10.1182/blood-2004-10-4047. Epub 2005 May 12.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology*
  • Antibody Formation*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Malaria / immunology*
  • Malaria / parasitology
  • Merozoite Surface Protein 1 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Plasmodium chabaudi / immunology

Substances

  • Antibodies, Protozoan
  • Merozoite Surface Protein 1