%0 Journal Article %A Donnarumma, Tiziano %A Young, George R %A Merkenschlager, Julia %A Eksmond, Urszula %A Bongard, Nadine %A Nutt, Stephen L %A Boyer, Claude %A Dittmer, Ulf %A Le-Trilling, Vu Thuy Khanh %A Trilling, Mirko %A Bayer, Wibke %A Kassiotis, George %D 2020 %T Opposing development of cytotoxic and follicular helper CD4 T cells controlled by the TCF-1-Bcl6 nexus %U 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 %2 https://crick.figshare.com/ndownloader/files/23930636 %K CD4 T cell differentiation %K adenovirus-based vaccination %K antiviral immunity %K cytotoxic CD4 T cells %K inhibitory receptors %K retroviral infection %K single-cell RNA sequencing %K Animals %K Cell Cycle Checkpoints %K Granzymes %K Mice %K Proto-Oncogene Proteins c-bcl-6 %K Retroviridae %K T Cell Transcription Factor 1 %K T-Lymphocytes, Cytotoxic %K T-Lymphocytes, Helper-Inducer %K Transcription, Genetic %K Kassiotis FC001099 %K Stoye FC001162 %K FC-ack %K AS-ack %K 0601 Biochemistry and Cell Biology %X 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. %I The Francis Crick Institute