Farkas L, Kvale E O, Lund-Johansen F, Jahnsen F L
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), Institute of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway.
Scand J Immunol. 2006 Oct;64(4):404-11. doi: 10.1111/j.1365-3083.2006.01792.x.
Inherent properties of dendritic cell (DC) subsets are important in the regulation of naïve T-cell differentiation (e.g. Th1 versus Th2 cells), whereas effector memory T cells are believed to produce a fixed cytokine repertoire independent of the type of antigen presenting cell. Here we show that two distinct human DC subsets, plasmacytoid DC (PDC) and myeloid CD11c+ DC, induced autologous mumps virus-specific memory CD4(+) T cells to produce markedly different cytokine patterns upon antigen stimulation. PDC stimulated the T cells to produce gamma-interferon (IFN-gamma) and interleukin-(IL)-10, whereas CD11c+ DC induced lower levels of IFN-gamma, virtually no IL-10, but significant levels of IL-5. Analysis of intracellular cytokine production showed simultaneous production of IL-10 and IFN-gamma in mumps-specific T cells activated by PDC, a cytokine pattern similar to that described for Th1-like regulatory cells. Introduction of CpG oligodeoxynucleotides in PDC/T-cell co-cultures had synergistic effect on virus-dependent IFN-gamma production, whereas the other cytokines remained unchanged. Together, our results show that the type of DC involved in reactivation of previously primed T cells may have significant impact on the resulting cytokine response and suggest that targeting of viral antigens and adjuvant to specific DC subsets should be considered in the design of therapeutic antiviral vaccines.
树突状细胞（DC）亚群的固有特性在调节初始T细胞分化（如Th1细胞与Th2细胞）中很重要，而效应记忆T细胞被认为会产生固定的细胞因子谱，与抗原呈递细胞的类型无关。在此我们表明，两种不同的人类DC亚群，浆细胞样DC（pDC）和髓样CD11c+ DC，在抗原刺激后可诱导自体腮腺炎病毒特异性记忆CD4(+) T细胞产生明显不同的细胞因子模式。pDC刺激T细胞产生γ干扰素（IFN-γ）和白细胞介素-（IL）-10，而CD11c+ DC诱导产生较低水平的IFN-γ，几乎不产生IL-10，但产生显著水平的IL-5。细胞内细胞因子产生分析显示，在由pDC激活的腮腺炎特异性T细胞中同时产生IL-10和IFN-γ，这种细胞因子模式类似于Th1样调节细胞所描述的模式。在pDC/T细胞共培养物中引入CpG寡脱氧核苷酸对病毒依赖性IFN-γ产生具有协同作用，而其他细胞因子保持不变。总之，我们的结果表明，参与先前致敏T细胞再激活的DC类型可能对产生的细胞因子反应有重大影响，并表明在治疗性抗病毒疫苗设计中应考虑将病毒抗原和佐剂靶向特定DC亚群。
