Production of human suppressor T cell hybridomas.
To study human T cell suppression of immunoglobulin (Ig) synthesis with homogeneous populations of immunoregulatory cells, human suppressor T cell hybridomas were prepared by somatic cell fusion of concanavalin A-activated peripheral blood T cells with hypoxanthine-guanine phosphoribosyltransferase-(HGPRT, EC 2.4.2.8) deficient human leukemic CEM T cells. After selection in hypoxanthine-aminopterin-thymidine (HAT) medium and cloning by limiting cell dilution, two human T cell hybridomas were identified that produced 60 to 80% suppression of in vitro polyclonal immunoglobulin production when cocultured with pokeweed mitogen- (PWM) stimulated peripheral blood lymphocytes. Further, one of the suppressor T cell hybridomas constitutively secreted a soluble suppressor factor(s) (TsF) of m.w. 70,000 to 85,000 daltons, which produced reversible noncytotoxic inhibition of lectin-activated B cell Ig production. In contrast, this TsF did not inhibit lectin- or antigen-induced T cell proliferation, nor did it interfere with the generation or effector function of cytotoxic T cells. Additional studies indicated that this Tsf acts directly on B cells or monocytes rather than indirectly modulating the activity of immunoregulatory T cells. In summary, these studies suggest that techniques of somatic cell fusion may provide a valuable approach to further study human immunoregulatory cell-cell interactions as well as provide a source of sufficient quantities of important lymphokines for further purification and characterization.
D002455:Cell Division; D002459:Cell Fusion; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000166:cytology / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis; D007158:Immunologic Techniques; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis; D010641:Phenotype; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013491:Suppressor Factors, Immunologic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology
D007136:Immunoglobulins; D008222:Lymphokines; D011043:Pokeweed Mitogens; D013491:Suppressor Factors, Immunologic