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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
Summary
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.
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.