Autogenic thymocytotoxic IgG antibody in normal guinea pigs

Normal guinea pig serum (GPS) was confirmed to be cytotoxic for guinea pig thymocytes at 4 degrees C. Approximately 50% of the cells were sensitive for the cytotoxic action of GPS (4 h incubation). Binding of IgG and, to a smaller extent, IgM to the thymocyte surface was shown after incubation with GPS. Absorption of GPS with protein A agarose (which removes immunoglobulins), heat inactivation (56 degrees C, which removes complement activity) or treatment with 2-mercaptoethanol (2-me) (which affected binding of IgG and IgM to thymocytes) abolished the cytotoxic activity. After gel filtration chromatography with Sephadex G-150, the cytotoxic activity was found in fractions with molecular weights comparable to that of IgG. This is different from reports of others on natural thymocytotoxic antibodies (NTA) where IgM was found to be the dominant thymocytotoxic antibody. The toxic activity in GPS was readily absorbed by autogenic bone marrow, spleen, lymph node and thymus cells. In contrast to normal thymocytes, mitogen stimulated thymus cells were totally resistant to the cytotoxic activity. In summary, it is suggested that the thymocytotoxic activity in GPS at 4 degrees C is mediated by IgG and complement and is directed against immature thymocytes. The antigenic determinant is also present on cells in other lymphoid organs.