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Natural and activated cytotoxic lymphocytes which act on autologous and allogeneic tumor cells
Authors:Eva Klein  Farkas Vánky
Institution:(1) Department of Tumor Biology, Karolinska Institute, S-104 01 Stockholm;(2) Radiumhemmet, Karolinska Hospital, S-104 01 Stockholm, Sweden
Abstract:Summary A considerable proportion of human blood lymphocytes that express natural cytotoxic potential belong to the T subset. They are heterogenous with regard to their surface receptor characteristics. Results obtained with the exceptionally sensitive cell lines (such as K562, Molt-4) and freshly harvested cells as targets reveal different types of cytotoxicity. While certain cell lines may be killed without the involvement of antigen recognition, the freshly harvested cells are recognized and killed by lymphocytes that carry receptors for surface antigens on these targets. In accordance, such tests can reveal the cytotoxicity of T cells that carry receptors for histocompatibility antigens. In view of the high frequency of these cells in the lymphocyte population, enlargement of the clone is not always necessary and activation suffices.Cytotoxicity against autologous tumor cells derived from surgical specimens of sarcomas and carcinomas was demonstrated only in a few patients when the blood lymphocytes were used directly after collection. Cytotoxic cells could be generated in a proportion of cases when a stimulus was given, e.g., co-cultivation with allogeneic lymphocytes in the conventional MLC test. Co-cultivation of autologous lymphocytes and tumor biopsy cells was the most efficient measure for the generation of auto-tumor cytotoxicity. This condition allows the enlargement of the reactive clone. When this was inhibited, e.g., by the presence of interferon in the mixed culture no auto-tumor killing was generated.We would like to emphasize that tumor cells seem not to share the membrane properties of the in vitro model lines, which exhibit high sensitivity to the natural or activated killer cells without the involvement of antigen recognition.
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