Antibodies directed at mouse IL-2-R alpha and beta chains act in synergy to abolish T-cell proliferation in vitro and delayed type hypersensitivity reaction in vivo.
The anti-mouse IL-2-R beta chain mAb TM-beta 1 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 alpha chain mAbs both in vitro and in vivo. In vitro, when associated at equimolar concentrations, the TM-beta 1/anti-alpha 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-alpha mAb alone. In addition, a bispecific antibody in which a Fab' fragment of TM-beta 1 was covalently linked to a Fab' fragment of one of the anti-alpha mAb (5A2) was shown to be as efficient as the TM-beta 1/5A2 association. The association of TM-beta 1 with 5A2 was also tested in vivo in a sheep red blood cell-induced delayed type hypersensitivity (DTH) model. TM-beta 1 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.
François
C
C
INSERM U-211, Institut de Biologie, Nantes, France.
Dantal
J
J
Sorel
M
M
Cherel
M
M
Miyasaka
M
M
Soulillou
J P
JP
Jacques
Y
Y
D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002460:Cell Line; D005260:Female; D006968:Hypersensitivity, Delayed; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2