Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107; and.
Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111.
J Immunol. 2018 May 15;200(10):3347-3352. doi: 10.4049/jimmunol.1701568. Epub 2018 Apr 11.
Numerous attempts to produce antiviral vaccines by harnessing memory CD8 T cells have failed. A barrier to progress is that we do not know what makes an Ag a viable target of protective CD8 T cell memory. We found that in mice susceptible to lethal mousepox (the mouse homolog of human smallpox), a dendritic cell vaccine that induced memory CD8 T cells fully protected mice when the infecting virus produced Ag in large quantities and with rapid kinetics. Protection did not occur when the Ag was produced in low amounts, even with rapid kinetics, and protection was only partial when the Ag was produced in large quantities but with slow kinetics. Hence, the amount and timing of Ag expression appear to be key determinants of memory CD8 T cell antiviral protective immunity. These findings may have important implications for vaccine design.
利用记忆 CD8 T 细胞生产抗病毒疫苗的尝试屡遭失败。进展的一个障碍是，我们不知道是什么使 Ag 成为保护性 CD8 T 细胞记忆的可行靶标。我们发现，在易受致死性小鼠痘（人类天花的小鼠同源物）感染的小鼠中，当感染病毒大量且快速地产生 Ag 时，诱导记忆 CD8 T 细胞的树突状细胞疫苗可完全保护小鼠。当 Ag 以少量产生时，即使动力学迅速，也不会发生保护作用，而当 Ag 大量产生但动力学缓慢时，保护作用仅部分发生。因此，Ag 表达的量和时间似乎是记忆 CD8 T 细胞抗病毒保护免疫的关键决定因素。这些发现可能对疫苗设计具有重要意义。
