Characterization of CD8+ T cells in immune-privileged organs of ZIKV-infected Ifnar1-/- mice
Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T-cell immunity in IPOs in Ifnar1-/- mice, based on an immunodominant epitope E294-302 tetramer. The distinct kinetics and functions of virus-specific CD8+ T cell infiltrated into different IPOs were characterized. The E294-302-specific TCRaßs are featured within the IPOs in different infection phases with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains. Specific chemokine receptors, Ccr2 and Ccr5, were selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-orientated migration of virus-specific T cells after infection. Overall, this study adds to the understanding of virus-specific CD8+ T cell responses for controlling and clearing ZIKV infection in IPOs. Overall design: We applied E294–302 tetramer selection to dissect virus-specific CD8+ T cells within different tissues of ZIKV infected Ifnar1-/- mice, including spleen, PBMCs, brain and testicle, at different onset times (7 and 30 dpi), and then performed single TCR sequencing and single-cell RNA sequencing (scRNA-seq) with 10× Genomics platform. Moreover, we also sequenced TCRs of general CD8+ T cells from the spleen at 0 dpi. After quality control processing and removing non-T cells, 40,371 high-quality single T cells were retained for the downstream analysis.