Opposing development of cytotoxic and follicular helper CD4 T cells controlled by the TCF-1-Bcl6 nexus
journal contributionposted on 2020-07-17, 16:37 authored by Tiziano Donnarumma, George R Young, Julia Merkenschlager, Urszula Eksmond, Nadine Bongard, Stephen L Nutt, Claude Boyer, Ulf Dittmer, Vu Thuy Khanh Le-Trilling, Mirko Trilling, Wibke Bayer, George Kassiotis
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 differentiationadenovirus-based vaccinationantiviral immunitycytotoxic CD4 T cellsinhibitory receptorsretroviral infectionsingle-cell RNA sequencingAnimalsCell Cycle CheckpointsGranzymesMiceProto-Oncogene Proteins c-bcl-6RetroviridaeT Cell Transcription Factor 1T-Lymphocytes, CytotoxicT-Lymphocytes, Helper-InducerTranscription, GeneticKassiotis FC001099Stoye FC001162FC-ackAS-ack0601 Biochemistry and Cell Biology