title: Reversal of experimental allergic encephalomyelitis with non-mitogenic, non-depleting anti-CD3 mAb therapy with a preferential effect on T(h)1 cells that is augmented by IL-4.
abstract: This study examined whether therapy with a non-mitogenic, non-activating anti-CD3 mAb (G4.18) alone, or in combination with the T(h)2 cytokines, could inhibit induction or facilitate recovery from experimental allergic encephalomyelitis (EAE) in Lewis rats. G4.18, but not rIL-4, rIL-5 or anti-IL-4 mAb, reduced the severity and accelerated recovery from active EAE. A combination of rIL-4 with G4.18 was more effective than G4.18 alone. The infiltrate of CD4(+) and CD8(+) T cells, B cells, dendritic cells, and macrophages in the brain stem was less with combined G4.18 and IL-4 than G4.18 therapy or no treatment. Residual cells had preferential sparing of T(r)1 cytokines IL-5 and transforming growth factor-beta with loss of T(h)1 markers IL-2, IFN-gamma and IL-12Rbeta2, and the T(h)2 cytokine IL-4 as well as macrophage cytokines IL-10 and tumor necrosis factor-alpha. Lymph nodes draining the site of immunization had less mRNA for T(h)1 cytokines, but T(h)2 and T(r)1 cytokine expression was spared. Treatment with G4.18, rIL-4 or rIL-5 from the time of immunization had no effect on the course of active EAE. MRC OX-81, a mAb that blocks IL-4, delayed onset by 2 days, but had no effect on severity of active EAE. G4.18 also inhibited the ability of activated T cells from rats with active EAE to transfer passive EAE. This study demonstrated that T cell-mediated inflammation was rapidly reversed by a non-activating anti-CD3 mAb that blocked effector T(h)1 cells, and spared cells expressing T(h)2 and T(r)1 cytokines.
authors.affiliation: Department of Medicine, University of New South Wales, Liverpool Hospital, Lock Mail Bag 7103, Liverpool BC, NSW 1871, Australia.
authors.forename: G T
authors.initials: GT
authors.lastname: Tran
authors.forename: N
authors.initials: N
authors.lastname: Carter
authors.forename: X Y
authors.initials: XY
authors.lastname: He
authors.forename: T S
authors.initials: TS
authors.lastname: Spicer
authors.forename: K M
authors.initials: KM
authors.lastname: Plain
authors.forename: M
authors.initials: M
authors.lastname: Nicolls
authors.forename: B M
authors.initials: BM
authors.lastname: Hall
authors.forename: S J
authors.initials: SJ
authors.lastname: Hodgkinson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001933:Brain Stem / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology*; D004357:Drug Synergism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D007116:Immunization, Passive; D015847:Interleukin-4 / Q000276:immunology / Q000627:therapeutic use*; D015848:Interleukin-5 / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D015848:Interleukin-5; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D015847:Interleukin-4