Natural killing target antigens as inducers of interferon: studies with an immunoselected, natural killing-resistant human T lymphoblastoid cell line

The human T lymphoblastoid cell line CEM was subjected to immunoselection by co-culture with peripheral blood mononuclear cells (PBMC) for resistance to natural killer (NK) cell-mediated lysis. The NK susceptibility of the resulting subline, CEM.NKR, was 8.4 to 20.6% of that of CEM when PBMC or adherent cell-depleted PBMC were used as effector cells, and -7.1 to 12.1% of that of CEM when Percoll gradient-enriched large granular lymphocytes (LGL) were used. However, CEM and CEM.NKR exhibited comparable sensitivity to antibody-dependent cellular cytotoxicity. Unlabeled CEM was eight- to 32-fold more effective than unlabeled CEM.NKR in inhibiting the NK lysis of labeled CEM target cells, and CEM bound 1.9 to 3.9-fold more Percoll gradient-enriched LGL than CEM.NKR in single cell-binding assays, suggesting that the NK-resistant variant has lost the expression of NK target antigens. However, CEM.NKR was comparable to CEM in its ability to induce interferon (IFN)-alpha production by PBMC in vitro, and the NK-resistant variant maintained its susceptibility to the antiproliferative effects of IFN-alpha, indicating that these phenomena may be mediated by molecules other than NK target structures. Comparison of CEM and CEM.NKR by indirect immunofluorescence with monoclonal antibodies specific for leukocyte antigens and the transferrin receptor, and by microcytotoxicity typing for HLA-A and B specificities, revealed no major differences.