Antibodies directed at mouse IL-2-R α and β chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo

Abstract

Abstract The anti-mouse IL-2-R P chain mAb TM-β1 which, by itself, does not affect IL-2-dependent proliferation through the high affinity mouse IL-2 receptor, was shown to cooperate in a synergistic way with a set of anti-IL-2-R α chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-β1/anti-α mAb association was four to ten times more efficient at inhibiting the proliferation of the CTL-L2 cell line than was a similar concentration of anti-α mAb alone. In addition, α bi-specific antibody in which a Fab' fragment of TM-P1 was covalently linked to a Fab' fragment of one of the anti-α mAb (5A2) was shown to be as efficient as the TM-PIISA2 association. The association of TM-β1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-P1 which, by itself, had no effect on DTH, induced a two- to threefold decrease in the doses of 5A2 required to suppress this cell-mediated immune reaction.