| Title: |
Memory CD8+ T cells exhibit tissue imprinting and nonstable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections |
| Authors: |
Shaw, Tovah; Haley, Michael; Dookie, Rebecca; Godfrey, Jenna J.; Cheeseman, Antonn; Strangward, Patrick; Zeef, Leo; Villegas-Mendez, Ana; Couper, Kevin |
| Source: |
Shaw, T, Haley, M, Dookie, R, Godfrey, J J, Cheeseman, A, Strangward, P, Zeef, L, Villegas-Mendez, A & Couper, K 2021, 'Memory CD8+ T cells exhibit tissue imprinting and nonstable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections', Immunology. |
| Publication Year: |
2021 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Description: |
Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterised 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 are 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0019-2805; 1365-2567 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pissn/0019-2805; info:eu-repo/semantics/altIdentifier/eissn/1365-2567 |
| Availability: |
https://research.manchester.ac.uk/en/publications/cf8f24b8-7c65-4efd-8905-1357d975cd3c |
| Rights: |
info:eu-repo/semantics/closedAccess |
| Accession Number: |
edsbas.7A61F174 |
| Database: |
BASE |