Mathieu Mélissa, Duval Frédéric, Daudelin Jean-François, Labrecque Nathalie
Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada; Department of Microbiology, Infectiology and Immunology, University of Montreal, Montreal, Quebec H3T 1J4, Canada; and.
Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec H1T 2M4, Canada;
J Immunol. 2015 Jun 15;194(12):5654-62. doi: 10.4049/jimmunol.1402837. Epub 2015 May 13.
Following an infection, naive CD8(+) T cells expand and differentiate into two main populations of effectors: short-lived effector cells (SLECs) and memory precursor effector cells (MPECs). There is limited understanding of the molecular mechanism and cellular processes governing this cell fate. Notch is a key regulator of cell fate decision relevant in many immunological pathways. In this study, we add to the role of Notch in cell fate decision and demonstrate that the Notch signaling pathway controls the MPEC/SLEC differentiation choice following both Listeria infection and dendritic cell immunization of mice. Although fewer SLECs were generated, Notch deficiency did not alter the rate of memory CD8(+) T cell generation. Moreover, we reveal that the Notch signaling pathway plays a context-dependent role for optimal cytokine production by effector CD8(+) T cells. Together, our results unravel critical functions for the Notch signaling pathway during effector CD8(+) T cell differentiation.
感染后，初始CD8(+) T细胞扩增并分化为两个主要的效应细胞群体：短期效应细胞（SLEC）和记忆前体效应细胞（MPEC）。目前对于控制这种细胞命运的分子机制和细胞过程了解有限。Notch是细胞命运决定的关键调节因子，在许多免疫途径中发挥作用。在本研究中，我们进一步阐述了Notch在细胞命运决定中的作用，并证明Notch信号通路在小鼠感染李斯特菌和树突状细胞免疫后控制MPEC/SLEC分化选择。虽然产生的SLEC较少，但Notch缺陷并未改变记忆CD8(+) T细胞的生成速率。此外，我们发现Notch信号通路在效应CD8(+) T细胞产生最佳细胞因子方面发挥着依赖于环境的作用。总之，我们的结果揭示了Notch信号通路在效应CD8(+) T细胞分化过程中的关键功能。
