1. 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.
- Author
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Tran GT, Carter N, He XY, Spicer TS, Plain KM, Nicolls M, Hall BM, and Hodgkinson SJ
- Subjects
- Animals, Brain Stem immunology, Brain Stem pathology, Drug Synergism, Immunization, Passive, Interleukin-4 immunology, Interleukin-5 therapeutic use, Leukocytes, Mononuclear pathology, Mice, Mice, Inbred BALB C, Myelin Basic Protein immunology, Rats, Rats, Inbred Lew, Recombinant Proteins therapeutic use, Spinal Cord immunology, Spinal Cord pathology, Antibodies, Monoclonal therapeutic use, CD3 Complex immunology, Encephalomyelitis, Autoimmune, Experimental therapy, Interleukin-4 therapeutic use, Th1 Cells drug effects
- 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.
- Published
- 2001
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