Vieira P L, de Jong E C, Wierenga E A, Kapsenberg M L, Kaliński P
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Immunol. 2000 May 1;164(9):4507-12. doi: 10.4049/jimmunol.164.9.4507.
Dendritic cells (DC) are key initiators of primary immune responses. Myeloid DC can secrete IL-12, a potent Th1-driving factor, and are often viewed as Th1-promoting APC. Here we show that neither a Th1- nor a Th2-inducing function is an intrinsic attribute of human myeloid DC, but both depend on environmental instruction. Uncommitted immature DC require exposure to IFN-gamma, at the moment of induction of their maturation or shortly thereafter, to develop the capacity to produce high levels of IL-12p70 upon subsequent contact with naive Th cells. This effect is specific for IFN-gamma and is not shared by other IL-12-inducing factors. Type 1-polarized effector DC, matured in the presence of IFN-gamma, induce Th1 responses, in contrast to type 2-polarized DC matured in the presence of PGE2 that induce Th2 responses. Type 1-polarized effector DC are resistant to further modulation, which may facilitate their potential use in immunotherapy.
树突状细胞（DC）是初次免疫反应的关键启动者。髓样DC可分泌白细胞介素-12（IL-12），这是一种强大的Th1驱动因子，通常被视为促进Th1的抗原呈递细胞（APC）。在此我们表明，诱导Th1或Th2的功能都不是人类髓样DC的固有属性，而是两者都依赖于环境指令。未定向的未成熟DC在其成熟诱导时或之后不久需要接触干扰素-γ（IFN-γ），以便在随后与初始Th细胞接触时产生高水平IL-12p70的能力得以发展。这种效应对IFN-γ具有特异性，其他诱导IL-12的因子并不具备。在IFN-γ存在下成熟的1型极化效应DC诱导Th1反应，与之形成对比的是，在前列腺素E2（PGE2）存在下成熟的2型极化DC诱导Th2反应。1型极化效应DC对进一步的调节具有抗性，这可能有助于其在免疫治疗中的潜在应用。
