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

Nat Immunol. 2016 Apr;17(4):422-32. doi: 10.1038/ni.3410. Epub 2016 Mar 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arenaviridae Infections / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Chromatin Immunoprecipitation
  • Cytokines / immunology
  • Flow Cytometry
  • Gene Expression Profiling
  • Influenza A Virus, H1N1 Subtype
  • Interleukin-12 / immunology*
  • Interleukin-17 / immunology
  • Interleukin-2 / immunology*
  • Lymphocytic choriomeningitis virus
  • Mice
  • Orthomyxoviridae Infections / immunology
  • Positive Regulatory Domain I-Binding Factor 1
  • Real-Time Polymerase Chain Reaction
  • STAT4 Transcription Factor / immunology
  • STAT5 Transcription Factor / immunology
  • Sequence Analysis, RNA
  • Signal Transduction
  • T-Box Domain Proteins / immunology*
  • Transcription Factors / immunology*


  • Cytokines
  • Interleukin-17
  • Interleukin-2
  • Prdm1 protein, mouse
  • STAT4 Transcription Factor
  • STAT5 Transcription Factor
  • Stat4 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Interleukin-12
  • Positive Regulatory Domain I-Binding Factor 1