3 research outputs found
Memory CD8<sup>+</sup> T cells exhibit tissue imprinting and non-stable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections
Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by CD8(+) Tācell accumulation within the brain. Whilst the dynamics of CD8(+) Tācell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasiteāspecific CD8(+) T cells upon resolution of ECM is not understood. In this study, we show that memory OTāI cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbAāOVA infection. Whereas memory OTāI cells within the spleen and lung exhibited canonical central memory (Tcm) and effector memory (Tem) phenotypes, respectively, memory OTāI cells within the brain postāPbAāOVA infection displayed an enriched CD69(+)CD103(ā) profile and expressed low levels of Tābet. OTāI cells within the brain were excluded from shortāterm intravascular antibody labelling but were targeted effectively by longerāterm systemically administered antibodies. Thus, the memory OTāI cells were extravascular within the brain postāECM but were potentially not resident memory cells. Importantly, whilst memory OTāI cells exhibited strong reactivation during secondary PbAāOVA infection, preventing activation of new primary effector T cells, they had dampened reactivation during a fourth PbAāOVA infection. Overall, our results demonstrate that memory CD8(+) T cells are systemically distributed but exhibit a unique phenotype within the brain postāECM, and that their reactivation characteristics are shaped by infection history. Our results raise important questions regarding the role of distinct memory CD8(+) Tācell populations within the brain and other tissues during repeat Plasmodium infections
Memory CD8 + T cells exhibit tissue imprinting and nonāstable exposureādependent reactivation characteristics following bloodāstage Plasmodium berghei ANKA infections
From Wiley via Jisc Publications RouterHistory: received 2020-11-02, rev-recd 2021-08-09, accepted 2021-08-13, pub-electronic 2021-08-27Article version: VoRPublication status: PublishedFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265; Grant(s): G0900487, MR/R010099/1Abstract: Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by CD8+ Tācell accumulation within the brain. Whilst the dynamics of CD8+ Tācell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasiteāspecific CD8+ T cells upon resolution of ECM is not understood. In this study, we show that memory OTāI cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbAāOVA infection. Whereas memory OTāI cells within the spleen and lung exhibited canonical central memory (Tcm) and effector memory (Tem) phenotypes, respectively, memory OTāI cells within the brain postāPbAāOVA infection displayed an enriched CD69+CD103ā profile and expressed low levels of Tābet. OTāI cells within the brain were excluded from shortāterm intravascular antibody labelling but were targeted effectively by longerāterm systemically administered antibodies. Thus, the memory OTāI cells were extravascular within the brain postāECM but were potentially not resident memory cells. Importantly, whilst memory OTāI cells exhibited strong reactivation during secondary PbAāOVA infection, preventing activation of new primary effector T cells, they had dampened reactivation during a fourth PbAāOVA infection. Overall, our results demonstrate that memory CD8+ T cells are systemically distributed but exhibit a unique phenotype within the brain postāECM, and that their reactivation characteristics are shaped by infection history. Our results raise important questions regarding the role of distinct memory CD8+ Tācell populations within the brain and other tissues during repeat Plasmodium infections