Pearce Erika L, Shen Hao
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Immunol. 2007 Aug 15;179(4):2074-81. doi: 10.4049/jimmunol.179.4.2074.
Various signals during infection influence CD8 T cell memory generation, but these factors have yet to be fully defined. IL-12 is a proinflammatory cytokine that has been shown to enhance IFN-gamma-producing T cell responses and has been widely tested as a vaccine adjuvant. In this study, we show that IL-12-deficient mice generate a weaker primary CD8 T cell response and are more susceptible to Listeria monocytogenes infection, but have substantially more memory CD8 T cells and greater protective immunity against reinfection. Kinetic analyses show that in the absence of IL-12 there is a reduced contraction of Ag-specific CD8 T cells and a gradual increase in memory CD8 T cells as a result of increased homeostatic renewal. By signaling directly through its receptor on CD8 T cells, IL-12 influences their differentiation to favor the generation of fully activated effectors, but hinders the formation of CD8 T cell memory precursors and differentiation of long-term CD8 T cell memory(.) These results have implications for understanding memory T cell development and enhancing vaccine efficacy, and offer new insight into the role of IL-12 in coordinating the innate and adaptive immune response.
感染过程中的各种信号会影响CD8 T细胞记忆的产生，但这些因素尚未完全明确。白细胞介素-12（IL-12）是一种促炎细胞因子，已被证明可增强产生γ干扰素的T细胞反应，并作为疫苗佐剂进行了广泛测试。在本研究中，我们发现IL-12缺陷小鼠产生的初始CD8 T细胞反应较弱，且更易感染单核细胞增生李斯特菌，但具有更多的记忆性CD8 T细胞以及更强的抗再感染保护性免疫。动力学分析表明，在缺乏IL-12的情况下，抗原特异性CD8 T细胞的收缩减少，并且由于稳态更新增加，记忆性CD8 T细胞逐渐增多。通过直接作用于CD8 T细胞上的受体发出信号，IL-12影响其分化，有利于产生完全活化的效应细胞，但会阻碍CD8 T细胞记忆前体的形成以及长期CD8 T细胞记忆的分化。这些结果对于理解记忆性T细胞的发育和提高疫苗效力具有重要意义，并为IL-12在协调固有免疫和适应性免疫反应中的作用提供了新的见解。
