Monitoring HLA-A2-restricted T cell responses and BCLA-specific serostatus during human latent Toxoplasma gondii infection suggests the implication of CD8+ T cells in parasite containment.

Abstract

T cells are critical to control Toxoplasma gondii (T. gondii) parasite infection. Yet, our understanding of T. gondii-specific CD8+ T cell responses in humans remains scarce. Here, we studied 56 HLA-A2+ healthy blood donors, including 40 latently infected subjects. In addition to routine T. gondii serodiagnosis, we quantified IgG specific for the bradyzoite-restricted Brain Cyst Load-associated Antigen (BCLA) and we enumerated blood-circulating parasite-specific CD8+ T cells by IFN-γ ELISPOT using a panel of 29 T. gondii peptides, previously reported to be HLA-A2 ligands. We identified a set of 16 epitopes that stimulates detectable CD8+ T cell responses in 50% routine T. gondii seropositive subjects, yet none was a universal immunodominant T. gondii epitope. Among individuals with either positive BCLA-specific serology and/or detectable T. gondii-specific T cell response, T. gondii-specific ELISPOT responses were inversely correlated with BCLA-specific IgG titers, suggesting that stronger CD8+ T cell responses may contribute to reduce chronic parasite burden or that certain long-standing infections may result in waning of antibody levels but persistence of CD8+ T cell memory. Furthermore, 2 out of 56 subjects displayed null T. gondii-specific humoral responses across 4 serological assays, but had measurable CD8+ T cell responses to 2 T. gondii peptides. This study sheds light on the complexity of T. gondii-specific immune responses in humans and rationalizes the cellular and serological toolkits for immune monitoring of latent T. gondii infection in humans.