Ben-Sasson S Z, Wang K, Cohen J, Paul W E
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892 Lautenberg Center for General and Tumor Immunology, The Hebrew University/Hadassah Medical Center, Jerusalem 91120, Israel.
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892.
Cold Spring Harb Symp Quant Biol. 2013;78:117-24. doi: 10.1101/sqb.2013.78.021246. Epub 2013 Oct 3.
Protective immune response requires massive expansion of antigen-triggered naïve cells, extensive differentiation into effector cells, migration of effectors into the periphery, and generation of a functional memory compartment. IL-1β strikingly enhances expansion of antigen-primed CD8 and CD4 T cells in vivo. Its T-cell expansion in lymph nodes and spleen was direct, requiring that the stimulated T cells express IL-1R1. Immunization in the presence of IL-1β increases the frequency of IL-17- and IFN-γ-producing cells among primed CD4 cells and the frequency of granzyme B-expressing and IFN-γ-producing cells and of cytotoxic cells among primed CD8 cells. IL-1β-induced increase in the number of the activated CD4 and CD8 cells and augmented differentiation of the antigen-triggered T cells is very pronounced in liver and lungs. CD4 and CD8 cells primed in the presence of IL-1β display augmented cell number and enhanced cytokine production when rechallenged 2 mo after priming with antigen and lipopolysaccharide (LPS). In five in vivo models, IL-1β enhanced the protective value of weak vaccines. Preliminary analysis of in vivo gene expression in CD4 cells stimulated with IL-1β revealed that IL-1β caused gene expression changes consistent with the up-regulation of pathways involved in cell replication, cell survival, and enhanced energy metabolism. Thus, IL-1β enhances antigen-primed CD4 and CD8 T-cell expansion, differentiation, and migration to the periphery and memory, the specific functions required for generation of effective protective immune responses.
保护性免疫反应需要大量扩增抗原触发的初始细胞，广泛分化为效应细胞，效应细胞迁移至外周，并产生功能性记忆细胞区室。IL-1β在体内显著增强抗原致敏的CD8和CD4 T细胞的扩增。其在淋巴结和脾脏中对T细胞的扩增是直接的，要求受刺激的T细胞表达IL-1R1。在IL-1β存在的情况下进行免疫接种，可增加致敏CD4细胞中产生IL-17和IFN-γ的细胞频率，以及致敏CD8细胞中表达颗粒酶B和产生IFN-γ的细胞频率和细胞毒性细胞频率。IL-1β诱导的活化CD4和CD8细胞数量增加以及抗原触发的T细胞分化增强在肝脏和肺中非常明显。在用抗原和脂多糖（LPS）致敏2个月后再次受到刺激时，在IL-1β存在下致敏的CD4和CD8细胞显示出细胞数量增加和细胞因子产生增强。在五个体内模型中，IL-1β增强了弱疫苗的保护作用。对用IL-1β刺激的CD4细胞进行体内基因表达的初步分析表明，IL-1β引起的基因表达变化与参与细胞复制、细胞存活和能量代谢增强的信号通路上调一致。因此，IL-1β增强了抗原致敏的CD4和CD8 T细胞的扩增、分化以及向外周和记忆的迁移，这些是产生有效的保护性免疫反应所需的特定功能。
