Normal guinea pig serum (GPS) kills subpopulations of rat thymus and bone marrow cells. The nonspecific cytotoxic reaction can be abrogated by heating the serum at 56°C or by adding either 0.01M EDTA or cobra venom factor and is, therefore, complement (C) dependent. C activity was found to be provided via the alternative pathway since serum from C4-deficient guinea pigs was also effective, and heating at 50°C for 20 min to destroy the activity of factor B inhibited its cytotoxicity. Furthermore the reaction was Mg++ but not Ca++ dependent.

Absorption with rat thymocytes in the presence of 0.01M EDTA failed to affect the cytotoxicity of GPS tested after restoration of Mg++. Similar absorptions performed in the presence of Mg++ did remove the cytotoxic activity. Gammaglobulins isolated from GPS lacked cytotoxicity when tested in the presence of normal rat serum as a source of C. These results are consistent with an antibody-independent mechanism.

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