Cytotoxic Immune Cells with Specificity for Defined Soluble Antigens

Abstract

Abstract Antigen-coated target cells were specifically lysed (a) by spleen cells from mice that had been immunized against the antigen presented in a soluble form and (b) by non-immune mouse spleen cells in the presence of specific antibodies. In the immune cell cytotoxic system, which consists of antibody-producing cells (APC) and cytotoxic effector cells (CEC), limiting dilution assays showed that the APC were diluted out before the CEC so that the amount of antibody being produced in vitro was limiting the cytotoxicity. In the presence of optimal concentrations of antibody, CEC from immune and non-immune cells were equally effective, regardless of whether the immune cells and the antibody were of the same or of different specificity. In vitro cytotoxicity in the immune spleen cell system started after a lag period of about 3 hr and was depressed to about 50% after the cells had been treated with trypsin. The cytotoxic activity of non-immune spleen cells in the presence of antibody started without a lag period and was not affected by trypsin treatment of the cells. Both the immune and the non-immune cell cytotoxic system were blocked by unrelated antigen-antibody complexes. Antibody-complexed target cells were much more potent inhibitors than were soluble complexes. Small numbers of target cells heavily coated with antibody were as efficient in blocking as were larger numbers of target cells lightly coated with antibody. The inhibition by antibodycomplexed antigen-coated target cells was neutralized by the addition of soluble antigen. This “unblocking” was thought to be due to a competition between soluble and insoluble antigen for antibody and the creation of non-inhibitory soluble complexes. The relevance of these findings for anti-tumor immune systems is discussed.