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

• Published in: International immunology Vol. 13; no. 9; p. 1109
• Main Authors: Tran, G T, Carter, N, He, X Y, Spicer, T S, Plain, K M, Nicolls, M, Hall, B M, Hodgkinson, S J
• Format: Journal Article
• Language: English
• Published: England 01.09.2001
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Brain Stem - immunology; Brain Stem - pathology; CD3 Complex - immunology; Drug Synergism; Encephalomyelitis, Autoimmune, Experimental - therapy; Immunization, Passive; Interleukin-4 - immunology; Interleukin-4 - therapeutic use; 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; Th1 Cells - drug effects
• ISSN: 0953-8178
• DOI: 10.1093/intimm/13.9.1109

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.