NF kappa B-Pim-1-Eomesodermin axis is critical for maintaining CD8 T-cell memory quality

作者：Knudson Karin M; Pritzl Curtis J; Saxena Vikas; Altman Amnon; Daniels Mark A; Teixeiro Emma^*

来源：Proceedings of the National Academy of Sciences, 2017, 114(9): E1659-E1667.

DOI：10.1073/pnas.1608448114

• CD8 T-cell memory
• NFkB
• Pim1
• Eomesodermin

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 NF kappa B signaling. Failure to maintain NF kappa B 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 NF(kappa)Bdependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NF kappa B and Eomes. T cells defective in TCR-dependent NF kappa B signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NF kappa B signaling was restored. We also found that NF kappa B-Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NF kappa B-Pim-1Eomes axis regulates Eomes levels to maintain memory fitness.

• 出版日期2017-2-28