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Department of Immunopathology, Scripps Clinic and Research Foundation, La Jolla, California 92037
Abstract
The target specificities of natural killer (NK) cells induced in mice by lymphocytic choriomeningitis virus (LCMV) were examined. All continuous and early passage cell lines tested were lysed by LCMV-induced NK cells, regardless of the target cell's origin (syngeneic, allogeneic, xenogeneic) or morphology (epithelia, fibroblast, lymphoblast, neuroblast, teratoma). Continuous cell line targets were lysed by LCMV- or vaccinia virus-induced NK cells from all tested strains of mice. Some target cells were more sensitive to lysis than other targets, but this relative sensitivity did not vary with the strain of mouse donating the effectors or with the time after inducing NK cells by the virus infection. LCMV-induced NK cells did not appear to recognize LCMV antigens on the surface of infected cells, nor could any correlation be made between retrovirus antigen expression and susceptibility to lysis. In contrast to this apparent lack of specificity in lysing continuous cell lines, we confirmed that some specificity could be demonstrated by using cold target inhibition experiments.
When primary peritoneal cells were used as targets, LCMV-induced NK cells from different strains of mice had restricted ranges of target specificities. NK cells from most homozygous mice lysed heterologous cells at much higher efficiency than isologous cells, but susceptibility to lysis was not directly related to H-2. In some strains of mice both isologous and heterologous targets were lysed. Spleen cells from F1 hybrid mice of certain strains lysed target cells from either parental strain. NK cell-mediated lysis of primary peritoneal cell targets did not require exogenous serum sources and was not significantly influenced by the presence of unlabeled target cells with varied susceptibilities incorporated into cytotoxicity assays.
We hypothesize that there may be two types of recognition mechanisms of the NK cell population: one that is "nonspecific," resulting in the lysis of continuous or transformed cells, and another that is "specific," resulting in a more selective lysis of primary cells. The vague specificities sometimes demonstrated against continuous cell targets by cold target inhibition experiments could be explained if the continuous cell line targets also expressed the specific recognition sites found on primary cells.
Footnotes
1 This is Publication No. 1578 from the Department of Immunopathology, Scripps Clinic and Research Foundation, La Jolla, California. This work was supported by United States Public Health Grants AI 12438, NS 12428, AI 07007, AI 09484, AI 13779, and AI 00248.
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