Ito T, Amakawa R, Inaba M, Ikehara S, Inaba K, Fukuhara S
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
J Immunol. 2001 Mar 1;166(5):2961-9. doi: 10.4049/jimmunol.166.5.2961.
Based on the relative expression of CD11c and CD1a, we previously identified subsets of dendritic cells (DCs) or DC precursors in human peripheral blood. A CD1a(+)/CD11c(+) population (CD11c(+) DCs), also called myeloid DCs, is an immediate precursor of Langerhans cells, whereas a CD1a(-)/CD11c(-) population (CD11c(-) DCs), sometimes called lymphoid DCs but better known as plasmacytoid DCs, is composed of type I IFN (IFN-alpha beta)-producing cells. Here, we investigate the effects of IFN-alpha beta and IFN-gamma as well as other cytokines on CD11c(+) and CD11c(-) DC subsets, directly isolated from the peripheral blood, instead of in vitro-generated DCs. IFN-gamma and IFN-alpha, rather than GM-CSF, were the most potent cytokines for enhancing the maturation of CD11c(+) DCs. Incubation of CD11c(+) DCs with IFN-gamma also resulted in increased IL-12 production, and this IL-12 allowed DCs to increase Th1 responses by alloreactive T cells. In contrast, IFN-alpha did not induce IL-12 but, rather, augmented IL-10 production. IFN-alpha-primed matured CD11c(+) DCs induced IL-10-producing regulatory T cells; however, this process was independent of the DC-derived IL-10. On the other hand, IFN-alpha by itself neither matured CD11c(-) DCs nor altered the polarization of responding T cells, although this cytokine was a potent survival factor for CD11c(-) DCs. Unlike IFN-alpha, IL-3 was a potent survival factor and induced the maturation of CD11c(-) DCs. The IL-3-primed CD11c(-) DCs activated T cells to produce IL-10, IFN-gamma, and IL-4. Thus, CD11c(+) and CD11c(-) DC subsets play distinct roles in the cytokine network, especially their responses to IFNs.
基于CD11c和CD1a的相对表达，我们之前在人外周血中鉴定出了树突状细胞（DC）或DC前体的亚群。CD1a(+)/CD11c(+)群体（CD11c(+) DC），也称为髓样DC，是朗格汉斯细胞的直接前体，而CD1a(-)/CD11c(-)群体（CD11c(-) DC），有时称为淋巴样DC，但更熟知的名称是浆细胞样DC，由产生I型干扰素（IFN-αβ）的细胞组成。在此，我们研究了IFN-αβ、IFN-γ以及其他细胞因子对直接从外周血中分离出的CD11c(+)和CD11c(-) DC亚群的影响，而非体外生成的DC。IFN-γ和IFN-α，而非GM-CSF，是增强CD11c(+) DC成熟的最有效细胞因子。用IFN-γ孵育CD11c(+) DC也导致IL-12产生增加，并且这种IL-12使DC能够通过同种异体反应性T细胞增强Th1反应。相反，IFN-α不诱导IL-12，而是增加IL-10的产生。IFN-α预处理的成熟CD11c(+) DC诱导产生IL-10的调节性T细胞；然而，这个过程独立于DC衍生的IL-10。另一方面，IFN-α本身既不能使CD11c(-) DC成熟，也不会改变反应性T细胞的极化，尽管这种细胞因子是CD11c(-) DC的有效存活因子。与IFN-α不同，IL-3是一种有效的存活因子，并诱导CD11c(-) DC成熟。IL-3预处理的CD11c(-) DC激活T细胞产生IL-10、IFN-γ和IL-4。因此，CD11c(+)和CD11c(-) DC亚群在细胞因子网络中发挥着不同的作用，尤其是它们对IFN的反应。
