NFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-cell memory quality

T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory,...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2017-02, Vol.114 (9), p.E1659-E1667
Main Authors: Knudson, Karin M., Pritzl, Curtis J., Saxena, Vikas, Altman, Amnon, Daniels, Mark A., Teixeiro, Emma
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
CD8-Positive T-Lymphocytes - immunology
Immunologic Memory - immunology
Mice
Mice, Inbred C57BL
Moloney murine leukemia virus - immunology
NF-kappa B - immunology
PNAS Plus
Receptors, Antigen, T-Cell - immunology
Signal Transduction - immunology
T-Box Domain Proteins - immunology
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Summary:T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly,we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB–Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB–Pim-1–Eomes axis regulates Eomes levels to maintain memory fitness.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1608448114