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

Research output: Contribution to journalArticle

75 Citations (Scopus)

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
Externally publishedYes

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Merozoite Surface Protein 1
T-cells
Malaria
Antibody Formation
Parasites
T-Lymphocytes
Antibodies
T-Cell Antigen Receptor
Infection
Plasmodium chabaudi
Adoptive Transfer
Helper-Inducer T-Lymphocytes
Interferons
Transgenic Mice
Epitopes
B-Lymphocytes
Vaccines
Erythrocytes
Cells
Cytokines

ASJC Scopus subject areas

  • Hematology

Cite this

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

In: Blood, Vol. 106, No. 5, 01.09.2005, p. 1676-1684.

Research output: Contribution to journalArticle

Stephens, Robin ; Albano, Frank R. ; Quin, Stuart ; Pascal, Benjamin J. ; Harrison, Vicky ; Stockinger, Brigitta ; Kioussis, Dimitris ; Weltzien, Hans Ulrich ; Langhorne, Jean. / 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. In: Blood. 2005 ; Vol. 106, No. 5. pp. 1676-1684.
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