Ferreri N R, Herzog W R, Askenase P W
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510.
J Immunol. 1993 Mar 15;150(6):2102-11.
In the picryl chloride contact sensitivity system in mice, i.v. injections of trinitrobenzene sulfonic acid (TNBSA) prevents elicitation of delayed-type hypersensitivity reactions. This suppression is due in part to a non-specific, PG-dependent factor (TNBSA-F) that is induced by i.v. injection of TNBSA and is produced by pooled spleen and lymph node cells in vitro. Inasmuch as a role for lymphokines such as IL-2 has been postulated in delayed-type hypersensitivity, we determined the in vitro effects of TNBSA-F on the responsiveness of HT-2 target cells to IL-2. TNBSA-F induced a dose-dependent unresponsiveness of HT-2 cells to IL-2. The inhibitory activity was not present in supernatants from lymphoid cells of sham-treated mice. In the presence of indomethacin, spleen, and lymph node cells from TNBSA-immunized mice produced a factor whose activity was much reduced compared to TNBSA-F. This suggested that PG were required for TNBSA-F activity. However, PG alone did not induce the unresponsiveness because TNBSA-F but not sham-treated mice had inhibitory activity despite containing similar levels of PGE2. Rather, the combination of i.v. TNBSA injections and PG synthesis during production of TNBSA-F were required to produce a suppressive TNBSA-F. The inhibitory effect of TNBSA-F was not due to the presence of transforming growth factor-beta, soluble immune-response suppressor, INF-gamma, or JE in the factor preparation. Partial characterization showed a single peak of in vitro TNBSA-F activity (molecular mass approximately 35-55 kDa) by Sephadex G-200 gel filtration chromatography and by HPLC. In addition, TNBSA-F retained its activity after multiple cycles of freeze-thaw and heating for 1 h at 56 degrees C. The inhibitory effects of TNBSA-F on IL-2-induced proliferation suggest that suppression of delayed type hypersensitivity after i.v. administration of TNBSA may, in part, be due to a PG-dependent suppressor factor that inhibits the responsiveness of target cells to IL-2.
在小鼠的苦味酸接触敏感性系统中，静脉注射三硝基苯磺酸（TNBSA）可防止迟发型超敏反应的激发。这种抑制作用部分归因于一种非特异性的、依赖前列腺素（PG）的因子（TNBSA-F），它由静脉注射TNBSA诱导产生，并由体外培养的脾细胞和淋巴结细胞产生。鉴于白细胞介素-2（IL-2）等淋巴因子在迟发型超敏反应中被认为发挥作用，我们测定了TNBSA-F对HT-2靶细胞对IL-2反应性的体外影响。TNBSA-F诱导HT-2细胞对IL-2产生剂量依赖性的无反应性。假处理小鼠的淋巴细胞上清液中不存在这种抑制活性。在吲哚美辛存在的情况下，TNBSA免疫小鼠的脾细胞和淋巴结细胞产生一种因子，其活性与TNBSA-F相比大幅降低。这表明PG是TNBSA-F活性所必需的。然而，单独的PG不会诱导无反应性，因为尽管TNBSA-F和假处理小鼠含有相似水平的前列腺素E2（PGE2），但只有TNBSA-F具有抑制活性。相反，静脉注射TNBSA以及在TNBSA-F产生过程中进行PG合成，两者结合才能产生具有抑制作用的TNBSA-F。TNBSA-F的抑制作用并非由于因子制剂中存在转化生长因子-β、可溶性免疫反应抑制因子、干扰素-γ或JE。部分特性分析显示，通过Sephadex G-200凝胶过滤色谱法和高效液相色谱法（HPLC），体外TNBSA-F活性呈现单峰（分子量约为35 - 55 kDa）。此外，TNBSA-F在多次冻融循环以及在56℃加热1小时后仍保留其活性。TNBSA-F对IL-2诱导的增殖的抑制作用表明，静脉注射TNBSA后迟发型超敏反应的抑制可能部分归因于一种依赖PG的抑制因子，该因子抑制靶细胞对IL-2的反应性。
