CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria

PLoS Pathog. 2014 May 22;10(5):e1004135. doi: 10.1371/journal.ppat.1004135. eCollection 2014 May.

Abstract

To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA) infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anopheles
  • Blood / parasitology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Immunization, Secondary / methods*
  • Life Cycle Stages / immunology*
  • Liver / immunology
  • Liver / parasitology
  • Malaria / blood
  • Malaria / immunology
  • Malaria / parasitology
  • Malaria / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Plasmodium berghei / growth & development
  • Plasmodium berghei / immunology*
  • Plasmodium chabaudi
  • Plasmodium yoelii
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Sporozoites / immunology*

Substances

  • Receptors, Antigen, T-Cell

Grants and funding

This work was supported by grants from the Australian Research Council (FF776174, CE140100011, DP130102481) and the National Health and Medical Research Council of Australia (APP1016629, APP1059861). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.