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Related Experiment Videos

Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.

Andrew M Intlekofer1, Naofumi Takemoto, E John Wherry

  • 1Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Nature Immunology
|November 8, 2005
PubMed
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Transcription factors T-bet and eomesodermin are crucial for maintaining memory CD8(+) T cells and natural killer cells. These factors regulate interleukin 15 responsiveness, linking cell renewal to effector function.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Memory CD8(+) T cells exhibit cytokine-driven renewal and possess a latent effector program.
  • Both memory CD8(+) T cells and natural killer (NK) cells depend on interleukin 15 (IL-15) and share cytotoxic potential.

Purpose of the Study:

  • To investigate the role of transcription factors T-bet and eomesodermin in the development and function of IL-15-dependent immune cells.
  • To elucidate the molecular mechanisms linking memory CD8(+) T cell renewal and effector function.

Main Methods:

  • Utilized compound mutations in the genes encoding T-bet and eomesodermin in mice.
  • Assessed the populations of memory CD8(+) T cells and mature NK cells.
  • Analyzed cytotoxic effector programming and CD122 expression.

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Main Results:

  • Mice with T-bet and eomesodermin mutations were deficient in IL-15-dependent lineages, including memory CD8(+) T cells and mature NK cells.
  • These mutant cells displayed defective cytotoxic effector programming.
  • T-bet and eomesodermin were found to induce enhanced expression of CD122, the IL-15 receptor.

Conclusions:

  • T-bet and eomesodermin are essential transcription factors for the long-term maintenance and effector function of memory CD8(+) T cells.
  • These transcription factors connect the proliferative renewal of memory CD8(+) T cells with their cytotoxic potency by regulating IL-15 responsiveness.