Post-thymic Thpok-deficiency in CD4 T cells compromises control of Toxoplasma gondii infection

Abstract Toxoplasma gondii, an intracellular parasite, is estimated to chronically infect >25% of the world-wide human population. While generally kept in check by host immune system, reactivation infection can occur when individuals become immunocompromised, particularly with T cell deficiencies. Both CD4+ and CD8+ cells play significant roles controlling this parasite. The transcription factor Thpok, critical for commitment MHC Class II-restricted thymocytes CD4 lineage during thymic differentiation, but also plays a post-thymic role shaping effector function mature cells. Based on these findings, we interrogated how mice deletion Thpok manage chronic using gondii (“Toxo” hereafter). During acute infection, Thpok-deficient have equivalent expansion Toxo-specific compared WT littermate controls, undergone “cytotoxic diversion”, upregulation CD8 transcriptional program loss helper function. phase die (~3 weeks p.i. vs >12 WT) exhibit increased Toxo cysts brain littermates, suggesting deficient control This death early not simply due lack help, as II-deficient survive significantly longer into (~6 weeks, p.i.). data indicates that are far worse at than complete absence Studies currently progress address mechanism which Thpok-deficiency dysregulates parasite Intramural National Institutes Health