Enhancement of immunogenicity of JEG‐3 Cells by ectopic expression of HLA‐A*0201 and CD80

Abstract

The chorioncarcinoma cell line JEG‐3 escapes immunity by secretion of leukocyte inhibitory factor suppressing leukocyte proliferation. The cells lack expression of classical HLA alleles but express nonclassical HLA‐G, which binds to killer inhibitory receptor of natural killer cells, preventing cytolysis. We investigated whether JEG‐3 cells are capable of immune stimulation after introduction of classical HLA and T‐cell costimulatory signals. JEG‐3 cells were transduced with vectors for HLA‐A*0201 and/or CD80. Parental JEG‐3, or JEG‐3/A2, JEG‐3/CD80, or JEG‐3/A2/CD80 were used to stimulate allogeneic T cells. While parental JEG‐3 cells induced only marginal proliferation of resting T cells, HLA‐A2 or CD80 expressing JEG‐3 induced enhanced proliferation. Double transfectants were most efficient. This difference was more obvious when T cells were preactivated by PHA. T cell lines restimulated with JEG‐3 transfectants were characterized for expansion, phenotypes, and cytolytic activity. HLA‐A2 matched and nonmatched donors were compared. T cells stimulated with JEG‐3/A2 or JEG‐3/CD80 were cytolytic towards parental JEG‐3 cells. Again double positive JEG‐3/A2/CD80 induced highest cytolytic activity, most obvious in HLA‐nonmatched donors suggesting alloreactivity to HLA. Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by JEG‐3 cells when classical HLA and/or costimulatory signals are present on the cells.