title: Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor.
abstract: As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL-7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Nikhil S
authors.initials: NS
authors.lastname: Joshi
authors.forename: Weiguo
authors.initials: W
authors.lastname: Cui
authors.forename: Anmol
authors.initials: A
authors.lastname: Chandele
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: David R
authors.initials: DR
authors.lastname: Urso
authors.forename: James
authors.initials: J
authors.lastname: Hagman
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D007156:Immunologic Memory; D007239:Infections / Q000276:immunology / Q000382:microbiology / Q000821:virology; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D037181:Lectins, C-Type; D051379:Mice; D008817:Mice, Mutant Strains; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D015415:Biomarkers; D016207:Cytokines; D019409:Interleukin-15; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D020395:Receptors, Interleukin-7; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma