Lymphocyte Soluble Factor-Activated Cell-Mediated Cytotoxicity: The Role of Ia-Like Antigens in Activation and Cytolysis, and Their Relationship to Fc Receptor

Abstract

Abstract Rabbit antisera to the human B cell-specific surface antigen complex (27,000 and 33,000 m.w.) have been employed to investigate the role of Ia-like antigens in cell-mediated lympholysis induced by supernatants from cultures of human peripheral blood lymphocytes. A single treatment of T lymphocytes with anti-B cell serum plus complement totally eliminated CFM-induced CML. Decomplemented antiserum or IgG F(ab′)2 fragments present during the 6-day culture period blocked the generation of cytotoxic effector cells. Furthermore, cytotoxicity was inhibited by simply pretreating T lymphocytes with either decomplemented antiserum of F(ab′)2 fragments before exposure to CFM. The blocking effects of these antisera or their derivatives were also shown to occur during the cytolytic phase of CFM-induced CML. The effector cell in this type of cytotoxicity is known to possess receptors for the Fc portion of IgG. However, that this inhibitory effect was not due to binding of antibodies to the Fc receptor was shown in studies that demonstrate that F(ab′)2 fragments of these antisera inhibited cytotoxicity but did not interfere with EA rosette formation. This was further supported by the demonstration that pretreatment of the T lymphocyte with aggregated γ-globulin abrogated EA rosette formation but did not suppress cytotoxicity. Thus, the following information has been obtained from these studies: 1) Both the precursors of cytotoxic cells and the cytotoxic cell itself in CFM-induced CML bear Ia-like antigens; 2) Ia-like antigens are necessary in both the sensitization and cytolytic phases of this cytotoxicity; and 3) the Ia-like antigen represents a cell surface site on the effector cell that is distinct from the Fc receptor.