Memory CD8+ T cells exhibit tissue imprinting and non-stable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections

Tovah N. Shaw, Michael J. Haley, Rebecca S. Dookie, Jenna J. Godfrey, Antonn J. Cheeseman, Patrick Strangward, Leo A.H. Zeef, Ana Villegas-Mendez, Kevin N. Couper*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by CD8+ T-cell accumulation within the brain. Whilst the dynamics of CD8+ T-cell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasite-specific CD8+ T cells upon resolution of ECM is not understood. In this study, we show that memory OT-I cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbA-OVA infection. Whereas memory OT-I cells within the spleen and lung exhibited canonical central memory (Tcm) and effector memory (Tem) phenotypes, respectively, memory OT-I cells within the brain post-PbA-OVA infection displayed an enriched CD69+CD103 profile and expressed low levels of T-bet. OT-I cells within the brain were excluded from short-term intravascular antibody labelling but were targeted effectively by longer-term systemically administered antibodies. Thus, the memory OT-I cells were extravascular within the brain post-ECM but were potentially not resident memory cells. Importantly, whilst memory OT-I cells exhibited strong reactivation during secondary PbA-OVA infection, preventing activation of new primary effector T cells, they had dampened reactivation during a fourth PbA-OVA infection. Overall, our results demonstrate that memory CD8+ T cells are systemically distributed but exhibit a unique phenotype within the brain post-ECM, and that their reactivation characteristics are shaped by infection history. Our results raise important questions regarding the role of distinct memory CD8+ T-cell populations within the brain and other tissues during repeat Plasmodium infections.

Original languageEnglish
Number of pages17
JournalImmunology
Early online date18 Aug 2021
DOIs
Publication statusE-pub ahead of print - 18 Aug 2021

Keywords

  • brain
  • CD8 T cell
  • cerebral malaria
  • immune memory

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