Li T K, Fox B S
Department of Biological Chemistry, University of Maryland, Baltimore 21201.
J Immunol. 1993 Mar 1;150(5):1680-90.
PGE2 is an immunomodulator that selectively inhibits the production of lymphokines associated with Th1 cells (IL-2 and IFN-gamma) but not Th2 cells (IL-4 and IL-5). We examined the effect of PGE2 on the production of IL-3 and granulocyte-macrophage (GM)-CSF from murine Th1 and Th2 clones. When the T cells were stimulated with Ag and APC, PGE2 inhibited IL-3/GM-CSF production from 3 Th1 clones and 1 Th2 clone, but enhanced production from 3 Th2 clones. A more specific bioassay demonstrated that IL-3 production was differentially affected by PGE2 in the Th clones. These data suggested that the effect of PGE2 on IL-3 production is dependent, not on a property of the lymphokine, but on a property of the T cell. The responsiveness to PGE2 did not consistently differ between Th1 and Th2 cells, and the observed heterogeneity in the response of Th2 clones did not correlate with the ability to induce increases in intracellular [Ca2+]. However, we postulated that signaling differences between the clones might explain the varied responsiveness to PGE2. If so, then the mode of stimulation might be expected to activate different pathways and thus affect the PGE2-responsiveness. Stimulation with ionomycin induced variable levels of IL-3/GM-CSF from the T cell clones. APC-derived costimulation dramatically enhanced IL-3/GM-CSF; the cells which produced high levels in response to ionomycin alone were not detectably costimulating each other. Interestingly, PGE2 enhanced IL-3/GM-CSF (and IL-3 alone in at least some cases) from cells stimulated with ionomycin alone, demonstrating that the mode of stimulation affects the PGE2-responsiveness. Addition of APC not only enhanced lymphokine production, but also altered the PGE2-responsiveness of the Th1 cells. In these cells, PGE2 either inhibited IL-3 and GM-CSF production or had no effect, in no case was the lymphokine production enhanced by PGE2 as it had been with ionomycin alone. These data indicate that the presence of APC-derived costimulatory signals can alter the effect of PGE2 on Th cell lymphokine production.
前列腺素E2（PGE2）是一种免疫调节剂，它能选择性抑制与Th1细胞相关的淋巴因子（白细胞介素-2和干扰素-γ）的产生，但不影响Th2细胞（白细胞介素-4和白细胞介素-5）。我们研究了PGE2对小鼠Th1和Th2克隆产生白细胞介素-3和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的影响。当T细胞用抗原和抗原呈递细胞（APC）刺激时，PGE2抑制了3个Th1克隆和1个Th2克隆产生白细胞介素-3/GM-CSF，但增强了3个Th2克隆的产生。一种更特异的生物测定法表明，PGE2对Th克隆中白细胞介素-3的产生有不同的影响。这些数据表明，PGE2对白细胞介素-3产生的影响不是取决于淋巴因子的特性，而是取决于T细胞的特性。Th1和Th2细胞对PGE2的反应性并非始终不同，并且在Th2克隆中观察到的反应异质性与诱导细胞内[Ca2+]增加的能力无关。然而，我们推测克隆之间的信号差异可能解释了对PGE2的不同反应性。如果是这样，那么刺激方式可能会激活不同的途径，从而影响对PGE2的反应性。用离子霉素刺激可诱导T细胞克隆产生不同水平的白细胞介素-3/GM-CSF。APC衍生的共刺激显著增强了白细胞介素-3/GM-CSF；单独对离子霉素产生高水平反应的细胞彼此之间没有可检测到的共刺激作用。有趣的是，PGE2增强了单独用离子霉素刺激的细胞产生的白细胞介素-3/GM-CSF（至少在某些情况下单独增强白细胞介素-3），表明刺激方式影响对PGE2的反应性。添加APC不仅增强了淋巴因子的产生，还改变了Th1细胞对PGE2的反应性。在这些细胞中，PGE2要么抑制白细胞介素-3和GM-CSF的产生，要么没有作用，在任何情况下，PGE2都不会像单独用离子霉素刺激时那样增强淋巴因子的产生。这些数据表明，APC衍生的共刺激信号的存在可以改变PGE2对Th细胞淋巴因子产生的影响。
