Donnarumma, Tiziano Young, George R Merkenschlager, Julia Eksmond, Urszula Bongard, Nadine Nutt, Stephen L Boyer, Claude Dittmer, Ulf Le-Trilling, Vu Thuy Khanh Trilling, Mirko Bayer, Wibke Kassiotis, George Opposing development of cytotoxic and follicular helper CD4 T cells controlled by the TCF-1-Bcl6 nexus CD4+ T cells develop distinct and often contrasting helper, regulatory, or cytotoxic activities. Typically a property of CD8+ T cells, granzyme-mediated cytotoxic T cell (CTL) potential is also exerted by CD4+ T cells. However, the conditions that induce CD4+ CTLs are not entirely understood. Using single-cell transcriptional profiling, we uncover a unique signature of Granzyme B (GzmB)+ CD4+ CTLs, which distinguishes them from other CD4+ T helper (Th) cells, including Th1 cells, and strongly contrasts with the follicular helper T (Tfh) cell signature. The balance between CD4+ CTL and Tfh differentiation heavily depends on the class of infecting virus and is jointly regulated by the Tfh-related transcription factors Bcl6 and Tcf7 (encoding TCF-1) and by the expression of the inhibitory receptors PD-1 and LAG3. This unique profile of CD4+ CTLs offers targets for their study, and its antagonism by the Tfh program separates CD4+ T cells with either helper or killer functions. CD4 T cell differentiation;adenovirus-based vaccination;antiviral immunity;cytotoxic CD4 T cells;inhibitory receptors;retroviral infection;single-cell RNA sequencing;Animals;Cell Cycle Checkpoints;Granzymes;Mice;Proto-Oncogene Proteins c-bcl-6;Retroviridae;T Cell Transcription Factor 1;T-Lymphocytes, Cytotoxic;T-Lymphocytes, Helper-Inducer;Transcription, Genetic;Kassiotis FC001099;Stoye FC001162;FC-ack;AS-ack;0601 Biochemistry and Cell Biology 2020-07-17
    https://crick.figshare.com/articles/journal_contribution/Opposing_development_of_cytotoxic_and_follicular_helper_CD4_T_cells_controlled_by_the_TCF-1-Bcl6_nexus/12668471