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

Autor:	Ivanova DL; Department of Immunology and Microbiology, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Thompson SB; Department of Immunology and Microbiology, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Klarquist J; Department of Immunology and Microbiology, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Harbell MG; Department of Immunology and Microbiology, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Kilgore AM; Department of Immunology and Microbiology, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Lasda EL; Department of Biochemistry & Molecular Genetics, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Hesselberth JR; Department of Biochemistry & Molecular Genetics, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA., Hunter CA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Kedl RM; Department of Immunology and Microbiology, University of Colorado - Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: ross.kedl@cuanschutz.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Aug 29; Vol. 42 (8), pp. 112911. Date of Electronic Publication: 2023 Jul 29.
DOI:	10.1016/j.celrep.2023.112911
Abstrakt:	T-bet and FOXO1 are transcription factors canonically associated with effector and memory T cell fates, respectively. During an infectious response, these factors direct the development of CD8 + T cell 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 T cells are compromised in the absence of either T-bet or FOXO1. Thus, unlike responses to challenge with Listeria monocytogenes, productive CD8 + T cell 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, T cells undergoing clonal expansion. Collectively, our data show that subunit vaccine adjuvants elicit T cell responses dependent on transcription factors associated with effector and memory cell fates. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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