A reappraisal of the effects of monoclonal antibodies directed at T cell differentiation antigens.

We examined the effects of monoclonal antibodies (Abs) directed at T3 antigen (expressed on most post-thymic T cells), T4 antigen (helper/inducer subset) and T8 antigen (suppressor/cytotoxic subset). Anti-T3 induced interleukin-2 production and proliferation of peripheral blood mononuclear cells (PBM). Anti-T4 or T8 did not exhibit such properties. Addition of methylprednisolone (MP) or cyclosporine (CsA) to PBM activated with anti-T3 resulted in 79% and 88% suppression of proliferation, respectively. Neither anti-T4 nor anti-T8 mediated significant inhibition of anti-T3-induced proliferation. Primary mixed lymphocyte cultures (MLC) were variably affected by Abs. Anti-T3 augmented proliferation found in primary MLCs at 48 hr and had an inconsistent effect on the proliferative response found at 120-136 hr of culture. Primary cytotoxic T lymphocyte (CTL) generation was consistently suppressed by anti-T3, while natural killer (NK)-cell-like activity was augmented at 72 hr and suppressed after 136 hr of culture. Anti-T4 mediated a dose-dependent suppression of proliferation and CTL generation in the primary MLC and had minimal effect on the induction of NK-cell-like activity. At high concentrations (5000-1000 ng/ml), anti-T8 mediated modest inhibition of proliferation and of the induction of cytolytic activity. Alloimmune memory cells, generated in long-term primary MLCs, were activated by anti-T3 to exhibit specific secondary cytolytic activity and NK-cell-like activity in the absence of the original priming stimulus. Neither anti-T4 nor anti-T8, under identical experimental conditions, activated memory cells. When interrelated, our experimental findings indicated that: (1) the ultimate immunity elicited by anti-T3-T3 antigen interaction is critically dependent upon the immune potential of the cell assessed; (2) MP or CsA can inhibit PBM activation by anti-T3; and (3) anti-T4 might have a role as an immunosuppressant in renal graft recipients.