Cutting Edge: IL-12 inversely regulates T-bet and eomesodermin expression during pathogen-induced CD8+ T cell differentiation.
Cytokines are critical determinants for specification of lineage-defining transcription factors of CD4+ T cell subsets. Little is known, however, about how cytokines regulate expression of T-bet and eomesodermin (Eomes) in effector and memory CD8+ T cells. We now report that IL-12, a signature of cell-mediated immunity, represses Eomes while positively regulating T-bet in effector CD8+ T cells during infection with Listeria monocytogenes. After resolution of infection and abatement of IL-12 signaling, Eomes expression rises whereas T-bet expression declines in memory CD8+ T cells. Eomes becomes derepressed in effector cells by ablation of IL-12 signaling. In the absence of IL-12, the dynamics of clonal expansion and contraction are also perturbed. Together, these results reveal how a pathogen-associated signal, such as IL-12, could act as a switch, regulating appropriate clonal growth and decline while, in parallel, shaping a unique pattern of fate-determining transcription factors.
Takemoto
Naofumi
N
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Intlekofer
Andrew M
AM
Northrup
John T
JT
Wherry
E John
EJ
Reiner
Steven L
SL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000276:immunology; D000098815:T-bet Transcription Factor
C491198:Eomes protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12