title: Type-I IFN drives the differentiation of short-lived effector CD8+ T cells in vivo.
abstract: Two subsets of CD8(+)  T cells are generated early during an immune response; one of these subsets forms the memory pool, known as memory precursor effector cells (MPECs), identified by high expression of CD127 and low expression of KLRG1, whereas the other subset forms short-lived effector cells (SLECs) identified by low expression of CD127 and high expression of KLRG1. Here, we studied in vivo the role of type-I IFN in this fate decision. We found that under priming conditions dominated by type-I IFN, as observed in lymphocytic choriomeningitis virus (LCMV) infection, type-I IFN signaling directly impacted the regulation of T-bet and thus the early fate decision of CD8(+)  T cells. In the absence of type-I IFN signaling, CD8(+)  T cells failed to form SLECs but could form MPECs that give rise to functional memory CD8(+)  T cells. Together, these findings identify type-I IFN as an important factor driving SLEC differentiation and thus instructing the early division between the effector and memory precursor CD8(+)  T-cell pool.
authors.affiliation: Institute for Microbiology, ETH Zürich, Zürich, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wiesel
authors.forename: Josh
authors.initials: J
authors.lastname: Crouse
authors.forename: Gregor
authors.initials: G
authors.lastname: Bedenikovic
authors.forename: Andrew
authors.initials: A
authors.lastname: Sutherland
authors.forename: Nicole
authors.initials: N
authors.lastname: Joller
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000276:immunology; D007156:Immunologic Memory; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D058408:Th1-Th2 Balance; D014764:Viral Proteins / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D007370:Interferon Type I; D010446:Peptide Fragments; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus