Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.
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.
Intlekofer
Andrew M
AM
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Takemoto
Naofumi
N
Wherry
E John
EJ
Longworth
Sarah A
SA
Northrup
John T
JT
Palanivel
Vikram R
VR
Mullen
Alan C
AC
Gasink
Christopher R
CR
Kaech
Susan M
SM
Miller
Joseph D
JD
Gapin
Laurent
L
Ryan
Kenneth
K
Russ
Andreas P
AP
Lindsten
Tullia
T
Orange
Jordan S
JS
Goldrath
Ananda W
AW
Ahmed
Rafi
R
Reiner
Steven L
SL
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
C491199:EOMES protein, human; D019409:Interleukin-15; D015375:Receptors, Interleukin-2; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors