Roth T L, White K L, Thompson D L, Rahmanian S, Horohov D W
Department of Animal Science, LSU Agricultural Center, Baton Rouge.
J Reprod Fertil. 1992 Sep;96(1):309-22. doi: 10.1530/jrf.0.0960309.
The mechanism by which a horse conceptus-derived immunosuppressive factor (HCS) of M(r) > 100,000 inhibits lymphocyte proliferation was investigated. The factor was obtained from the culture supernatants of 20-day-old horse conceptuses; activity, identified by reduced uptake of [3H]thymidine by mitogen-stimulated lymphocytes, was greatest (P < 0.01) in cultures stimulated by mitogen from pokeweed. HCS also suppressed cell proliferation stimulated by phytohaemagglutinin (P < 0.01), but had no effect on lipopolysaccharide-stimulated cells (P > 0.05). Data from a fluorescence-activated cell sorter indicated that supplementation with HCS reduced the number of T cells in phytohaemagglutinin-stimulated cultures and suppressed proliferation of T and B cells in pokeweed-mitogen-stimulated cultures compared with controls. Cell proliferation was greater (P < 0.01) in cultures supplemented with HCS 24 h after stimulation than in those treated at the start of stimulation, and was even greater (P < 0.01) when cells were treated 48 h after stimulation. The removal of HCS from treated lymphocyte cultures resulted in complete recovery of cell responsiveness, and stimulated proliferation of treated cells did not differ (P > 0.05) from that of control cells. The addition of stimulated equine lymphocyte supernatant to cultures supplemented with HCS did not significantly increase (P > 0.05) cell proliferation in response to pokeweed mitogen. Addition of recombinant human interleukin 2 (rIL-2) to HCS-treated cultures did not alter the suppressive activity of HCS, although cell proliferation was greater in cultures supplemented with rIL-2 than in controls (P < 0.01). HCS inhibition of IL-2 receptor (IL-2R) function was investigated using an IL-2-dependent murine cytolytic T lymphocyte cell line; the fraction of HCS of M(r) > 100,000 had no effect (P > 0.05) on proliferation of IL-2-dependent murine cytolytic T lymphocyte cells induced by rIL-2. Together, these data suggest that HCS suppresses proliferation of T lymphocytes during the early stages of cell activation by inhibiting IL-2R interaction and that this suppression interferes with interactions between T cells and B cells, thereby also indirectly inhibiting proliferation of B cells. The potent immunosuppressive capacity of HCS may be one factor responsible for inhibiting cell-mediated fetal allograft rejection during pregnancy.
对分子量大于100,000的马胚胎衍生免疫抑制因子（HCS）抑制淋巴细胞增殖的机制进行了研究。该因子从20日龄马胚胎的培养上清液中获得；通过有丝分裂原刺激的淋巴细胞对[3H]胸苷摄取减少来鉴定活性，在商陆有丝分裂原刺激的培养物中活性最大（P<0.01）。HCS也抑制了植物血凝素刺激的细胞增殖（P<0.01），但对脂多糖刺激的细胞没有影响（P>0.05）。荧光激活细胞分选仪的数据表明，与对照组相比，添加HCS可减少植物血凝素刺激的培养物中T细胞的数量，并抑制商陆有丝分裂原刺激的培养物中T细胞和B细胞的增殖。刺激后24小时添加HCS的培养物中的细胞增殖比刺激开始时处理的培养物中的细胞增殖更大（P<0.01），当细胞在刺激后48小时处理时增殖甚至更大（P<0.01）。从处理过的淋巴细胞培养物中去除HCS导致细胞反应性完全恢复，并且处理过的细胞的刺激增殖与对照细胞的刺激增殖没有差异（P>0.05）。向添加HCS的培养物中添加刺激的马淋巴细胞上清液，对商陆有丝分裂原刺激的细胞增殖没有显著增加（P>0.05）。向HCS处理的培养物中添加重组人白细胞介素2（rIL-2）并没有改变HCS的抑制活性，尽管添加rIL-2的培养物中的细胞增殖比对照组更大（P<0.01）。使用依赖IL-2的小鼠细胞毒性T淋巴细胞系研究了HCS对IL-2受体（IL-2R）功能的抑制作用；分子量大于100,000的HCS部分对rIL-2诱导的依赖IL-2的小鼠细胞毒性T淋巴细胞的增殖没有影响（P>0.05）。总之，这些数据表明，HCS通过抑制IL-2R相互作用在细胞激活的早期阶段抑制T淋巴细胞的增殖，并且这种抑制干扰了T细胞和B细胞之间的相互作用，从而也间接抑制了B细胞的增殖。HCS强大的免疫抑制能力可能是孕期抑制细胞介导的胎儿同种异体移植排斥反应的一个因素。
