Kapasi K, Albert S E, Yie S, Zavazava N, Librach C L
Division of Reproductive Science, The Toronto Hospital Research Institute, Department of Obstetrics and Gynecology, Women's College Hospital, University of Toronto, Toronto, Ont., Canada.
Immunology. 2000 Oct;101(2):191-200. doi: 10.1046/j.1365-2567.2000.00109.x.
Human leucocyte antigen (HLA) -G is expressed on trophoblast cells during pregnancy, suggesting a role in protection of the semiallogeneic fetus. Published data suggest that HLA-G protects a cell against natural killer cell lysis. It has been hypothesized that HLA-G may also protect the fetus by preventing allo-cytotoxic T lymphocyte (CTL) responses. To test this hypothesis, we assayed the effects of various concentrations of purified HLA-G on CTL response in a mixed lymphocyte culture (MLC) system. We found that concentrations > or =0.1 microg/ml of HLA-G suppressed the allo-CTL response by 30-100% over the control, but, paradoxically, concentrations of 0.01-0.05 microg/ml of HLA-G augmented the allo-CTL response by 25-50% over the control. Concentrations < or = 0.001 microg/ml HLA-G had no effect. Addition of HLA-G to preprimed allo-CTL effector cells did not affect their killing ability. Allo-CTL suppressive doses of HLA-G induced a T helper type 2 (Th2) cytokine response, whereas allo-CTL-enhancing doses of HLA-G induced a Th1-type cytokine response. HLA-G purified from first-trimester placenta does not affect allo-proliferative responses nor does it alter the percentage of CD4+ or CD8+ T cells in MLCs. These findings support a potential role for HLA-G-mediated suppression of allo-CTL formation in normal pregnancies. In addition, the effects observed at lower concentrations of HLA-G may have interesting implications for the condition of pre-eclampsia in which concentrations of this HLA class I molecule are reduced.
人类白细胞抗原（HLA）-G在孕期的滋养层细胞上表达，提示其在保护半同种异体胎儿方面发挥作用。已发表的数据表明，HLA-G可保护细胞免受自然杀伤细胞的裂解。据推测，HLA-G还可能通过阻止同种细胞毒性T淋巴细胞（CTL）反应来保护胎儿。为验证这一假说，我们在混合淋巴细胞培养（MLC）系统中检测了不同浓度的纯化HLA-G对CTL反应的影响。我们发现，HLA-G浓度≥0.1μg/ml时，与对照组相比，同种CTL反应受到30%-100%的抑制，但矛盾的是，HLA-G浓度为0.01-0.05μg/ml时，同种CTL反应比对照组增强了25%-50%。HLA-G浓度≤0.001μg/ml时无影响。将HLA-G添加到预先致敏的同种CTL效应细胞中并不影响其杀伤能力。HLA-G抑制同种CTL的剂量可诱导2型辅助性T细胞（Th2）细胞因子反应，而增强同种CTL的HLA-G剂量则诱导Th1型细胞因子反应。从孕早期胎盘纯化的HLA-G不影响同种增殖反应，也不改变MLC中CD4+或CD8+T细胞的百分比。这些发现支持了HLA-G介导的抑制正常妊娠中同种CTL形成的潜在作用。此外，在较低浓度HLA-G下观察到的效应可能对先兆子痫的病情具有有趣的意义，在先兆子痫中这种I类HLA分子的浓度会降低。
