Two Phenotypically Distinct Subsets of Spleen Dendritic Cells in Rats Exhibit Different Cytokine Production and T Cell Stimulatory Activity1
Two Phenotypically Distinct Subsets of Spleen Dendritic Cells in Rats Exhibit Different Cytokine Production and T Cell Stimulatory Activity1
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DOI：
10.4049/jimmunol.169.5.2284
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
C. Voisine;F. Hubert;B. Trinité;M. Heslan;R. Josien
中科院分区：
文献类型：
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作者：
C. Voisine;F. Hubert;B. Trinité;M. Heslan;R. Josien
我们最近报道，大鼠脾脏树突状细胞（DC）可以分为CD 4+和CD 4 −亚群，并且CD 4 −亚群在体外对肿瘤细胞表现出天然的细胞毒活性。此外，最近的一份报告表明，CD 4 − DC在体内可能具有致耐受性。在这项研究中，我们分析了新鲜分离的脾脏DC亚群的表型和体外T细胞刺激活性。与CD 4 −亚群不同，CD 4+脾DC表达CD 5、CD 90和信号调节蛋白α分子。新鲜的CD 4 −和CD 4 + DC都显示出不成熟的表型，尽管CD 4+细胞组成性表达中等水平的CD 80。在体外，CD 4 −而不是CD 4 + DC的半衰期非常短，但细胞可以被CD 40配体、IL-3或GM-CSF从死亡中拯救出来。CD 4 − DC产生大量的促炎细胞因子IL-12和TNF-α，并诱导同种异体CD 4 + T细胞的Th 1应答，而CD 4 + DC产生少量的IL-12，不产生TNF-α，但诱导Th 1和Th 2应答。与强烈刺激纯化的CD 8 + T细胞增殖的CD 4 + DC相比，CD 4 − DC表现出较差的CD 8 + T细胞刺激能力，其通过CD 40刺激而显著增加。因此，如先前在小鼠和人类中所示，我们已经确定了大鼠中存在诱导Th 1应答的高IL-12产生DC亚群。CD 4+和CD 4-DC亚群在病毒感染后均产生少量的IFN-α，这一事实表明它们与浆细胞样DC无关。
We recently reported that splenic dendritic cells (DC) in rats can be separated into CD4+ and CD4− subsets and that the CD4− subset exhibited a natural cytotoxic activity in vitro against tumor cells. Moreover, a recent report suggests that CD4− DC could have tolerogenic properties in vivo. In this study, we have analyzed the phenotype and in vitro T cell stimulatory activity of freshly isolated splenic DC subsets. Unlike the CD4− subset, CD4+ splenic DC expressed CD5, CD90, and signal regulatory protein α molecules. Both fresh CD4− and CD4+ DC displayed an immature phenotype, although CD4+ cells constitutively expressed moderate levels of CD80. The half-life of the CD4−, but not CD4+ DC in vitro was extremely short but cells could be rescued from death by CD40 ligand, IL-3, or GM-CSF. The CD4− DC produced large amounts of the proinflammatory cytokines IL-12 and TNF-α and induced Th1 responses in allogeneic CD4+ T cells, whereas the CD4+ DC produced low amounts of IL-12 and no TNF-α, but induced Th1 and Th2 responses. As compared with the CD4+ DC that strongly stimulated the proliferation of purified CD8+ T cells, the CD4− DC exhibited a poor CD8+ T cell stimulatory capacity that was substantially increased by CD40 stimulation. Therefore, as previously shown in mice and humans, we have identified the existence of a high IL-12-producing DC subset in the rat that induces Th1 responses. The fact that both the CD4+ and CD4− DC subsets produced low amounts of IFN-α upon viral infection suggests that they are not related to plasmacytoid DC.