title: Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.
abstract: Two seemingly unrelated hallmarks of memory CD8(+) T cells are cytokine-driven proliferative renewal after pathogen clearance and a latent effector program in anticipation of rechallenge. Memory CD8(+) T cells and natural killer cells share cytotoxic potential and dependence on the growth factor interleukin 15. We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8(+) T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming. Moreover, T-bet and eomesodermin were responsible for inducing enhanced expression of CD122, the receptor specifying interleukin 15 responsiveness. Therefore, these key transcription factors link the long-term renewal of memory CD8(+) T cells to their characteristic effector potency.
authors.affiliation: Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Intlekofer
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takemoto
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Longworth
authors.forename: John T
authors.initials: JT
authors.lastname: Northrup
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Palanivel
authors.forename: Alan C
authors.initials: AC
authors.lastname: Mullen
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gasink
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Miller
authors.forename: Laurent
authors.initials: L
authors.lastname: Gapin
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ryan
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Russ
authors.forename: Tullia
authors.initials: T
authors.lastname: Lindsten
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.forename: Ananda W
authors.initials: AW
authors.lastname: Goldrath
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D000098815:T-bet Transcription Factor
chemical_list: C491199:EOMES protein, human; D019409:Interleukin-15; D015375:Receptors, Interleukin-2; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors