Modulation of in vitro lymphocyte transformation by antibodies: enhancement by antigen-antibody complexes and inhibition by antibody excess

The in vitro lymphoproliferative responses to diphtheria and tetanus toxoids by lymph node lymphocytes from guinea pigs immunized to manifest both antibody production and delayed hypersensitivity were inhibited by antisera to these antigens. These inhibitory effects were greater in the presence of fresh sera containing complement than in heat inactivated sera. The antitoxins interfered to a lesser extent with the lymphocyte response to phytohemagglutinin, purified protein derivative, bovine serum albumin, and dinitrophenol guinea pig albumin than with tetanus toxoid and were therefore not nonspecifically cytotoxic. After 60 min of exposure the inhibitory effects of the antisera could still be reversed by washing the lymphocytes free of antibodies and restimulating them with either of the toxoids. Conversely, partial inhibition by antitetanus was achieved even when the antiserum was added 18 hr after the tetanus toxoid. This suggests that even after initiation of the lymphocyte response to antigen it could be reversed by the addition of antibodies.Antigen-antibody (Ag-Ab) complexes were prepared and the precipitates separated from the supernatants. The supernatants of the Ag-Ab complexes in antibody excess often stimulated lymphocytes to a limited extent and concomitantly inhibited the lymphocyte from responding to any additional antigen. Supernatants of Ag-Ab complexes at equivalence and in antigen excess stimulated the lymphocytes more effectively. In contrast all the precipitated Ag-Ab complexes including those prepared in antibody excess stimulated the lymphocytes significantly and often up to twice as effectively as the uncomplexed antigen. The presence of fresh sera containing complement was not a prerequisite for obtaining lymphocyte stimulation with the precipitated complexes. The precipitated Ag-Ab complexes did not stimulate lymphocytes from unsensitized guinea pigs. These findings indicate that an excess of soluble antibodies can block the response of sensitized lymphocytes to specific antigens, whereas antigen aggregated by antibody could enhance the proliferative response. These in vitro studies suggest that antibodies can affect the cellular immune response by modulating the lymphoproliferative reaction to antigens.