title: Anti-interleukin 2 receptor monoclonal antibodies spare phenotypically distinct T suppressor cells in vivo and exert synergistic biological effects.
abstract: The therapeutic efficacies of ART-18, ART-65, and OX-39, mouse antibodies of IgG1 isotype recognizing distinct epitopes of the p55 beta chain of the rat IL-2-R molecule, were probed in LEW rat recipients of (LEW X BN)F1 heterotopic cardiac allografts (acute rejection in untreated hosts occurs within 8 d). A 10-d course with ART-18 prolongs graft survival to approximately 21 d (p less than 0.001). Therapy with ART-65, but not with OX-39, was effective (graft survival approximately 16 and 8 d, respectively). Anti-IL-2-R mAb treatment selectively spared T cells with donor-specific suppressor functions; the CD8+ (OX8+ W3/25-) fraction from ART-18-modified recipients, and primarily the CD4+ (W3/25+ OX8-) subset from ART-65-treated hosts conferred unresponsiveness to naive syngeneic rats after adoptive transfer, increasing test graft survival to approximately 16 and 45 d, respectively. Concomitant administration of ART-18 and ART-65 to recipient animals in relatively low doses exerted a strikingly synergistic effect, with 30% of the transplants surviving indefinitely and 50% undergoing late rejection over 50 d. These studies provide evidence that anti-IL-2-R mAbs selectively spare phenotypically distinct T cells with suppressor functions. The data also suggest that in vivo targeting of functionally different IL-2-R epitopes may produce synergistic biological effects.
authors.affiliation: Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: R
authors.initials: R
authors.lastname: Di Stefano
authors.forename: A
authors.initials: A
authors.lastname: Mouzaki
authors.forename: D
authors.initials: D
authors.lastname: Araneda
authors.forename: T
authors.initials: T
authors.lastname: Diamantstein
authors.forename: N L
authors.initials: NL
authors.lastname: Tilney
authors.forename: J W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000502:physiology*; D051381:Rats; D011971:Receptors, Immunologic / Q000276:immunology*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2