Koc Serpil, Kather Angela, Markert Udo R, Dürst Matthias, Schneider Achim, Kaufmann Andreas M
Abteilung für Frauenheilkunde, Gynäkologische Molekularbiologie, Frauenklinik, FSU Jena, Jena, Germany.
Am J Reprod Immunol. 2003 Sep;50(3):243-53. doi: 10.1034/j.1600-0897.2003.00072.x.
The choriocarcinoma cell line Jeg3 suppresses immunity in vitro by secretion of soluble factors like leukemia inhibitory factor suppressing leukocyte activation. The cells lack expression of classical human leukocyte antigen (HLA)-A and -B alleles but express some HLA-C, and non-classical HLA-G and -E. Upon binding to killing inhibitory receptor on natural killer (NK) cells, HLA-G prevents activation of cytolytic activity. We investigated whether Jeg3 cells are capable of immune stimulation after complementation with classical HLA and T cell costimulatory signal CD80.
Jeg3 cells were transduced to express HLA-A*0201 and/or CD80. Parental Jeg3 or transfectants Jeg3-A2, Jeg3-CD80 or Jeg3-CD80-A2 were used to stimulate allogeneic resting and activated peripheral blood lymphocytes (PBL). The different cell lines were loaded with a HLA-A2-restricted Epstein-Barr virus (EBV) recall antigen peptide epitope and antigen presenting ability was examined. T cell lines specific for Jeg3 and transfectants were generated from HLA-A2 matched and nonmatched donors and compared for expansion, phenotypes and cytolytic activity.
While all Jeg3 cell lines induced only marginal proliferation of resting T cells, phytohemagglutinin (PHA)-activated T cells were stimulated by CD80 or CD80-A2 expressing Jeg3. Only the transfectant Jeg3-CD80-A2 was capable of specific T cell stimulation by EBV recall antigen presentation. T cell lines of HLA-A2 non-matched donors stimulated with the Jeg3 transfectants showed significant expansion only when HLA-A2 and the costimulus CD80 were present. T cells from HLA-A2 positive donors did not expand significantly or differentially. No NK cells grew under any condition. In Jeg3-CD80-A2 stimulated T cells lines CD8+ cells expanded preferentially. These T cells exerted cytolytic activity toward all Jeg3 cell lines.
Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by Jeg3 cells when classical HLA- and/or costimulatory signals are present on the cells.
绒癌细胞系Jeg3通过分泌可溶性因子（如抑制白细胞激活的白血病抑制因子）在体外抑制免疫。这些细胞缺乏经典人类白细胞抗原（HLA）-A和-B等位基因的表达，但表达一些HLA-C以及非经典的HLA-G和-HLA-E。HLA-G与自然杀伤（NK）细胞上的杀伤抑制受体结合后，可阻止细胞溶解活性的激活。我们研究了Jeg3细胞在与经典HLA和T细胞共刺激信号CD80互补后是否具有免疫刺激能力。
将Jeg3细胞转导以表达HLA-A*0201和/或CD80。使用亲本Jeg3或转染子Jeg3-A2、Jeg3-CD80或Jeg3-CD80-A2刺激同种异体静息和活化的外周血淋巴细胞（PBL）。用HLA-A2限制性EB病毒（EBV）回忆抗原肽表位加载不同细胞系，并检测抗原呈递能力。从HLA-A2匹配和不匹配的供体中产生针对Jeg3和转染子的T细胞系，并比较其扩增、表型和细胞溶解活性。
虽然所有Jeg3细胞系仅诱导静息T细胞的少量增殖，但表达CD80或CD80-A2的Jeg3可刺激植物血凝素（PHA）激活的T细胞。只有转染子Jeg3-CD80-A2能够通过EBV回忆抗原呈递进行特异性T细胞刺激。用Jeg3转染子刺激的HLA-A2不匹配供体的T细胞系仅在存在HLA-A2和共刺激信号CD80时才显示出显著扩增。来自HLA-A2阳性供体的T细胞没有显著扩增或差异扩增。在任何条件下都没有NK细胞生长。在Jeg3-CD80-A2刺激的T细胞系中，CD8+细胞优先扩增。这些T细胞对所有Jeg3细胞系都具有细胞溶解活性。
我们的数据表明，尽管存在免疫抑制机制，但当细胞上存在经典HLA和/或共刺激信号时，Jeg3细胞可诱导增殖性和细胞溶解性T细胞反应。
