Effector memory Th1 CD4 T cells are maintained in a mouse model of chronic malaria

Robin Stephens, Jean Langhorne

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Protection against malaria often decays in the absence of infection, suggesting that protective immunological memory depends on stimulation. Here we have used CD4+ T cells from a transgenic mouse carrying a T cell receptor specific for a malaria protein, Merozoite Surface Protein-1, to investigate memory in a Plasmodium chabaudi infection. CD4+ memory T cells (CD44hiIL-7Rα+) developed during the chronic infection, and were readily distinguishable from effector (CD62LloIL- 7Rα-) cells in acute infection. On the basis of cell surface phenotype, we classified memory CD4+ T cells into three subsets: central memory, and early and late effector memory cells, and found that early effector memory cells (CD62LloCD27+) dominated the chronic infection. We demonstrate a linear pathway of differentiation from central memory to early and then late effector memory cells. In adoptive transfer, CD44hi memory cells from chronically infected mice were more effective at delaying and reducing parasitemia and pathology than memory cells from drug-treated mice without chronic infection, and contained a greater proportion of effector cells producing IFN-γ and TNFα, which may have contributed to the enhanced protection. These findings may explain the observation that in humans with chronic malaria, activated effector memory cells are best maintained in conditions of repeated exposure.

Original languageEnglish (US)
Article numbere1001208
JournalPLoS Pathogens
Volume6
Issue number11
DOIs
StatePublished - Nov 2010

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T-Lymphocytes
Malaria
Infection
Plasmodium chabaudi
Merozoite Surface Protein 1
Immunologic Memory
Acute malaria
Parasitemia
Adoptive Transfer
T-Cell Antigen Receptor
Transgenic Mice
Pathology
Phenotype
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Effector memory Th1 CD4 T cells are maintained in a mouse model of chronic malaria. / Stephens, Robin; Langhorne, Jean.

In: PLoS Pathogens, Vol. 6, No. 11, e1001208, 11.2010.

Research output: Contribution to journalArticle

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