Dynamics of antigen re-exposure to CD8+ T cells during Toxoplasma gondii infection

Abstract

Abstract The role of T cell Receptor (TCR) stimulation in activation, expansion, and eventual exhaustion of CD8+ T cells has been well characterized in multiple mouse models of disease. What has not been well characterized is the dynamics of antigen re-exposure to CD8+ T cells in non-lymphoid tissues throughout disease progression, and what proportion of CD8+ T cells have been re-stimulated by antigen at any given time. To answer this question, Nur77-GFP reporter OT-I mice were utilized, which provides a sensitive fluorescent reporter for recent TCR stimulation. In mice infected with a transgenic version of the parasite Toxoplasma gondii expressing OVA, the response of Nur77-GFP OT-I to this stimulus was assessed during the acute and chronic phases of infection. Data from these experiments showed that TCR stimulation varies between infected tissues, but largely correlated with infectious burden. For example, during acute infection, up to 50% of the OT-I in the brain had recently re-encountered antigen whereas during the chronic phase approximately 15% of the OT-I expressed Nur77-GFP. Furthermore, characterization of Nur77GFP+ versus Nur77-GFP− OT-I revealed a role of TCR stimulation in co-expression of the inhibitory receptors Tim3 and PD-1. This model system provides a better understanding of how frequently pathogen specific T cells re-encounter cognate antigen and future studies will focus on the role antigen re-exposure plays in CD8+ T cell effector function and memory formation.