Effects of anti-CD3 monoclonal antibodies on functional activity of lymphocytes: Studies in vivo and in vitro

Lymphocyte functional activity was tested in 38 renal transplant recipients receiving induction treatment with various anti-CD3 MoAbs, i.e. OKT3, T3.G2a (an IgG2a anti-CD3 MoAb) or T3.A (an IgA anti-CD3 MoAb of the same idiotype). During treatment with OKT3 and T3.G2a, lymphocyte response to phytohaemagglutinin-P (PHA), as determined with the use of a whole-blood lymphocyte culture technique, decreased significantly. However, during treatment with T3.A PHA response was not affected. Using a conventional lymphocyte culture technique, PHA response was unchanged during treatment with all three MoAbs, indicating that the immunosuppressive effect of OKT3 and T3.G2a is probably dependent upon the presence of MoAb in culture medium and is reversible. In addition, we tested in vitro inhibition of aspecific mitogen- or antigen-induced lymphocyte stimulation by OKT3, T3.A and T3.G2a. It appeared that at low concentrations (<25 ng/ml) T3.G2a and OKT3 exerted a stronger immunosuppressive effect than T3.A. However, at higher concentrations T3.A, OKT3 and T3.G2a were equally immunosuppressive. We conclude that the immunosuppressive effect of T3.A is caused by blindfolding. At low concentrations T3.G2a exerts its immunosuppressive effect mainly through modulation of the CD3 and/or T cell receptor complex, as a result of interaction with Fc receptors on monocytes. At higher concentrations blindfolding of the CD3/T cell receptor complex may contribute to immunosuppression.