title: Rheumatoid arthritis T cells produce Th1 cytokines in response to stimulation with a novel trispecific antibody directed against CD2, CD3, and CD28.
abstract: Rheumatoid arthritis (RA) T cells respond poorly to conventional mitogens. We have examined the proliferative and cytokine responses of T cells to a synthetic trispecific antibody (Tsab) directed against CD2, CD3, and CD28. In 11 subjects RA T cells proliferated more, and secreted significantly more IL-2, in response to Tsab than did control peripheral blood (PB) cells. Very high levels of IL-2 were produced by 2 patients with aggressive disease. Measurement of intracellular IL-2, IFN-gamma, IL-4, and IL-5 by flow cytometry showed a Th1 pattern of cytokine production in 13 RA and 9 control subjects. We conclude that RA T cells are not irreversibly inactivated, and that spatial arrangement of stimulating molecules may be important in eliciting maximal responses.
authors.affiliation: Rheumatology Department, Southampton General Hospital, Southampton University Hospitals NHS Trust, UK. rayw@cwcom.net
authors.forename: W M
authors.initials: WM
authors.lastname: Wong
authors.forename: S A
authors.initials: SA
authors.lastname: Vakis
authors.forename: K R
authors.initials: KR
authors.lastname: Ayre
authors.forename: C N
authors.initials: CN
authors.lastname: Ellwood
authors.forename: W M
authors.initials: WM
authors.lastname: Howell
authors.forename: A L
authors.initials: AL
authors.lastname: Tutt
authors.forename: M I
authors.initials: MI
authors.lastname: Cawley
authors.forename: J L
authors.initials: JL
authors.lastname: Smith
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D018801:CD2 Antigens / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D013582:Synovial Fluid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D008934:Mitogens