Vercammen C, Ceuppens J L
Cell Immunol. 1987 Jan;104(1):24-36. doi: 10.1016/0008-8749(87)90003-7.
We have studied the effects of prostaglandin E2 (PGE2) on in vitro human T-cell activation induced by crosslinking of the CD3-Ti complex with the monoclonal anti-CD3 antibodies OKT3 and UCHT-1. PGE2 (greater than or equal to 3 X 10(-9) M) when added simultaneously with anti-CD3 to cultures of peripheral blood mononuclear cells (PBMC), significantly suppressed, in a dose-dependent way, T-cell proliferation (P less than 0.002). However, when T cells were first preactivated with OKT3 for 3 days, subsequent proliferation driven by recombinant interleukin 2 (IL-2) was not inhibited by addition of PGE2. This indicates that PGE2 affects the activation step resulting from crosslinking of CD3-Ti, but not the IL-2-driven proliferative phase. Other manifestations of T-cell activation were therefore examined. Both IL-2 production and the expression of receptors for IL-2 (as detected with the anti-Tac monoclonal antibody) were inhibited by PGE2. The addition of purified interleukin 1 (IL-1) or recombinant IL-2 to the cultures did not reverse the inhibiting effect of PGE2 on IL-2-receptor expression. PGE2, added at the time of culture initiation, also inhibited T-cell proliferation in cultures which were supplemented with exogenous IL-1 or IL-2. Proof for a direct effect of PGE2 on T cells was obtained in experiments in which monocyte-depleted T cells were stimulated, in the presence of IL-1, with solid-phase-bound anti-CD3 antibody. Proliferation of T cells in this system is accessory cell independent and still was strongly inhibited by PGE2. Finally, preincubation of PBMC with PGE2 (3 X 10(-6) M) for 48 hr did not result in the generation of suppressor cells for anti-CD3-induced T-cell proliferation or for IL-2 production. Our results demonstrate that PGE2 has a direct inhibitory effect on an early step of T-cell activation, resulting in decreased IL-2 production, decreased IL-2-receptor expression, decreased responsiveness to exogenous IL-2, and decreased proliferation. However, PGE2 does not affect IL-2-driven proliferation of activated T cells. The inhibitory effect on T-cell activation is not mediated through suppressor T cells, nor through inhibition of accessory cell function.
我们研究了前列腺素E2（PGE2）对用单克隆抗CD3抗体OKT3和UCHT-1交联CD3-Ti复合物诱导的体外人T细胞活化的影响。当与抗CD3同时加入外周血单核细胞（PBMC）培养物中时，PGE2（大于或等于3×10^(-9) M）以剂量依赖的方式显著抑制T细胞增殖（P<0.002）。然而，当T细胞先用OKT3预激活3天时，随后由重组白细胞介素2（IL-2）驱动的增殖不受PGE2添加的抑制。这表明PGE2影响CD3-Ti交联导致的活化步骤，但不影响IL-2驱动的增殖阶段。因此，我们检查了T细胞活化的其他表现。PGE2抑制IL-2的产生和IL-2受体的表达（用抗Tac单克隆抗体检测）。向培养物中添加纯化的白细胞介素1（IL-1）或重组IL-2并不能逆转PGE2对IL-2受体表达的抑制作用。在培养开始时添加的PGE2也抑制了补充有外源性IL-1或IL-2的培养物中的T细胞增殖。在用IL-1存在下用固相结合的抗CD3抗体刺激单核细胞耗尽的T细胞的实验中，获得了PGE2对T细胞直接作用的证据。该系统中T细胞的增殖不依赖辅助细胞，且仍受到PGE2的强烈抑制。最后，用PGE2（3×10^(-6) M）预孵育PBMC 48小时，并未导致产生针对抗CD3诱导的T细胞增殖或IL-2产生的抑制细胞。我们的结果表明，PGE2对T细胞活化的早期步骤具有直接抑制作用，导致IL-2产生减少、IL-2受体表达减少、对外源性IL-2的反应性降低以及增殖减少。然而，PGE2不影响活化T细胞的IL-2驱动的增殖。对T细胞活化的抑制作用不是通过抑制性T细胞介导的，也不是通过抑制辅助细胞功能介导的。
