A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet Academic Article uri icon

abstract

  • T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8(+) T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8(+) T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8(+) T cell differentiation.

authors

  • Xin, A
  • Masson, F
  • Liao, Y
  • Preston, S
  • Guan, T
  • Gloury, R
  • Olshansky, M
  • Lin, J-X
  • Li, P
  • Speed, TP
  • Smyth, GK
  • Ernst, M
  • Leonard, WJ
  • Pellegrini, M
  • Kaech, SM
  • Nutt, SL
  • Shi, W
  • Belz, GT
  • Kallies, A

publication date

  • 2016

has subject area