Effects of interleukin 2 receptor b chain (P75)-specific monoclonal antibody on the generation of cytotoxic T lymphocytes and suppressor T cells in mixed lymphocyte culture.

The interaction of interleukin 2 (IL-2) with its receptor (IL-2R) plays an essential role in the proliferation and differentiation of T cells. The IL-2R beta-chain is considered to function directly in the intracellular signal transduction. In this study, we investigated using a newly established IL-2R beta-chain-specific monoclonal antibody (MAb) (TU-25) and an IL-2R alpha-chain-specific MAb (H-31). The IL-2-induced proliferation of concanavalin blasts and the mixed lymphocyte reaction (MLR) were suppressed by TU-25 in combination with H-31. This combination had a greater suppressive effect than each of them alone. The generation of cytotoxic T lymphocytes (CTL) using a cell-mediated lympholysis (CML) assay, was not inhibited by TU-25 alone. TU-25 in combination with H-31 suppressed the generation of CTL completely in this assay even if recombinant IL-2 (rIL-2) was added. Although the CTL generation was inhibited, cells that suppressed a fresh MLR were preserved. Our study suggests that the combination of TU-25 with H-31 completely blocks the functional high-affinity binding site of IL-2 but does not inhibit the generation of suppressor cells. This may lead to immunosuppressive therapy using an IL-2R beta-chain-specific MAb in combination with an IL-2R alpha-chain-specific MAb in clinical organ transplantation.