OKT3 induces suppressor cells for mixed lymphocyte and PHA mitogenic responses in human peripheral lymphocytes

Human peripheral lymphocytes pretreated with the Orthoclone monoclonal anti-T cell antibody OKT3 for 48 h markedly suppressed the proliferative response of autologous lymphocytes in one-way MLC and the mitogenic response to PHA. The ability to induce suppression is specific to OKT3 since other monoclonal antibodies to human T cells (OKT1, OKT4 and OKT8) did not elicit similar responses, OKT3 is mitogenic but further proliferation of OKT3 pretreated lymphocytes was not required for the suppression of autologous lymphocytes since mitomycin-C treated cells were fully effective. Kinetic studies indicated that pretreatment of lymphocytes with OKT3 for 24 h was sufficient to induce marked inhibition of the mitogenic response of autologous lymphocytes to PHA whereas suppression in MLC was not observed until lymphocytes were pretreated for 48 h. These studies support the previous observations that OKT3 may be reacting with an important molecule on the T cell surface and that interaction of OKT3 with this molecule induces profound functional changes.