Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1

Abstract

T-bet and FOXO1 are transcription factors canonically associated with effector and memory Tcell fates, respectively. During an infectious response, these factors direct the development of CD8+ Tcell fates, where T-bet deficiency leads to ablation of only short-lived effector cells, while FOXO1 deficiency results in selective loss of memory. In contrast, following adjuvanted subunit vaccination in mice, both effector- and memory-fated Tcells are compromised in the absence of either T-bet or FOXO1. Thus, unlike responses to challenge with Listeria monocytogenes, productive CD8+ Tcell responses to adjuvanted vaccination require coordinated regulation of FOXO1 and T-bet transcriptional programs. Single-cell RNA sequencing analysis confirms simultaneous T-bet, FOXO1, and TCF1 transcriptional activity in vaccine-elicited, but not infection-elicited,Tcells undergoing clonal expansion. Collectively, our data show that subunit vaccine adjuvants elicit Tcell responses dependent on transcription factors associated with effector and memory cell fates.