Tomar R S, Kerkvliet N I
Environmental Toxicology Graduate Program, University of California, Riverside 92521-0127.
Toxicol Lett. 1991 Jun;57(1):55-64. doi: 10.1016/0378-4274(91)90119-q.
Antibody production to the T-dependent antigen SRBC is highly sensitive to suppression by polychlorinated dibenzo-p-dioxins. The present study provides evidence for a defect in T-helper (TH) cells in TCDD-exposed mice. Because spleen cells from nonimmune TCDD-exposed mice did not show suppressed antibody responses when adoptively transferred to irradiated hosts, we used a hapten-carrier (TNP-SRBC) system with cell separation/reconstitution techniques to determine the effects of TCDD on carrier-specific TH cells. In vitro cultures of spleen cells from SRBC-primed TCDD-treated (5 micrograms/kg) mice produced fewer anti-TNP plaque-forming cells (PFC) when immunized with TNP-SRBC, as compared to cells from primed vehicle-treated controls. A reduced anti-TNP PFC response was also observed in experiments where non-immune B-cells were induced to produce anti-TNP PFC by TH-cells obtained from carrier-primed TCDD-exposed mice, as compared to carrier-primed vehicle-exposed mice. Removal of Lyt-2+ (suppressor) T-cells in these experiments did not alter the anti-TNP PFC response. These results provide direct evidence for reduced activity of TH-cells after exposure to TCDD.
对T细胞依赖性抗原绵羊红细胞(SRBC)的抗体产生对多氯二苯并对二噁英的抑制高度敏感。本研究为暴露于2,3,7,8-四氯二苯并对二噁英(TCDD)的小鼠辅助性T(TH)细胞存在缺陷提供了证据。由于将未免疫的暴露于TCDD的小鼠的脾细胞过继转移至受辐照宿主时未显示出抗体反应受到抑制,因此我们使用半抗原-载体(三硝基苯磺酸-绵羊红细胞,TNP-SRBC)系统及细胞分离/重建技术来确定TCDD对载体特异性TH细胞的影响。与用赋形剂处理的致敏对照小鼠的细胞相比,用TNP-SRBC免疫时,来自经TCDD处理(5微克/千克)的SRBC致敏小鼠的脾细胞的体外培养物产生的抗TNP空斑形成细胞(PFC)较少。在实验中还观察到,与用赋形剂处理的载体致敏小鼠相比,由来自载体致敏的暴露于TCDD的小鼠获得的TH细胞诱导非免疫B细胞产生抗TNP PFC时,抗TNP PFC反应降低。在这些实验中去除Lyt-2 +(抑制性)T细胞并没有改变抗TNP PFC反应。这些结果为暴露于TCDD后TH细胞活性降低提供了直接证据。