Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+ T cell response during acute and chronic toxoplasmosis.

ABSTRACT

Initial TCR engagement (priming) of naive CD8+ T cells results in T cell expansion, and these early events influence the generation of diverse effector and memory populations. During infection, activated T cells can re-encounter cognate antigen, but how these events influence local effector responses or formation of memory populations is unclear. To address this issue, OT-I T cells which express the Nur77-GFP reporter of TCR activation were paired with the parasite Toxoplasma gondii that expresses OVA to assess how secondary encounter with antigen influences CD8+ T cell responses. During acute infection, TCR stimulation in affected tissues correlated with parasite burden and was associated with markers of effector cells while Nur77-GFP- OT-I showed signs of effector memory potential. However, both Nur77-GFP- and Nur77-GFP+ OT-I from acutely infected mice formed similar memory populations when transferred into naive mice. During the chronic stage of infection in the CNS, TCR activation was associated with large scale transcriptional changes and the acquisition of an effector T cell phenotype as well as the generation of a population of CD103+ CD69+ Trm like cells. While inhibition of parasite replication resulted in reduced effector responses it did not alter the Trm population. These data sets highlight that recent TCR activation contributes to the phenotypic heterogeneity of the CD8+ T cell response but suggest that this process has a limited impact on memory populations at acute and chronic stages of infection.