title: In vitro and in vivo inhibition of mitogen-driven T-cell activation by recombinant interferon beta.
abstract: Recombinant interferon beta (rIFN beta) is being tested as experimental immunotherapy for exacerbating-remitting MS. To clarify the possible mechanisms of a therapeutic response to rIFN beta in MS patients, we conducted studies on the effects of rIFN beta on mitogen-driven T-cell activation by stimulating peripheral blood mononuclear cells (PBMC) with concanavalin A (ConA) or with anti-CD3 monoclonal antibodies in the presence or absence of rIFN beta. We monitored T-cell activation using proliferation assays or by expression of surface activation markers detected by flow cytometry. In vitro rIFN beta, in concentrations > or = 10 U/ml, inhibited PBMC proliferation or surface expression of interleukin-2 receptor (IL-2R), transferrin receptor, or CD2. In contrast, rIFN gamma augmented mitogen-driven IL-2R expression. PBMC isolated from normal volunteers or MS patients responded to ConA and rIFN beta in a similar manner. We conducted pilot in vivo studies in exacerbating-remitting MS patients participating in a double-blind placebo-controlled clinical trial of rIFN beta. PBMC were isolated from study participants immediately before and 24 hours after a weekly study injection. IL-2R expression by T cells was determined following a ConA stimulus. While there was no significant change following placebo injection, rIFN beta recipients showed significantly reduced ConA-driven IL-2R expression following study injection. The results document in vitro and in vivo inhibition of mitogen-driven T-cell activation by rIFN beta. This suggests a possible mechanism underlying a therapeutic response to rIFN beta in MS patients.
authors.affiliation: Department of Neurology, Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, OH 44195.
authors.forename: R A
authors.initials: RA
authors.lastname: Rudick
authors.forename: C S
authors.initials: CS
authors.lastname: Carpenter
authors.forename: D L
authors.initials: DL
authors.lastname: Cookfair
authors.forename: V K
authors.initials: VK
authors.lastname: Tuohy
authors.forename: R M
authors.initials: RM
authors.lastname: Ransohoff
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018801:CD2 Antigens; D002478:Cells, Cultured; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D008934:Mitogens; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma