International Immunology, Vol. 13, No. 9, 1109-1120,
September 2001
© 2001 Japanese Society for Immunology
Reversal of experimental allergic encephalomyelitis with non-mitogenic, non-depleting anti-CD3 mAb therapy with a preferential effect on Th1 cells that is augmented by IL-4
Department of Medicine, University of New South Wales, Liverpool Hospital, Lock Mail Bag 7103, Liverpool BC, NSW 1871, Australia
1 Department of Medicine, University of Colorado, Denver, CO 80262 USA
Correspondence to: S. J. Hodgkinson
This study examined whether therapy with a non-mitogenic, non-activating anti-CD3 mAb (G4.18) alone, or in combination with the Th2 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 Tr1 cytokines IL-5 and transforming growth factor-ß with loss of Th1 markers IL-2, IFN-
and IL-12Rß2, and the Th2 cytokine IL-4 as well as macrophage cytokines IL-10 and tumor necrosis factor-
. Lymph nodes draining the site of immunization had less mRNA for Th1 cytokines, but Th2 and Tr1 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 Th1 cells, and spared cells expressing Th2 and Tr1 cytokines.
Keywords: anti-CD3, autoimmunity, experimental allergic encephalomyelitis, immunotherapy, multiple sclerosis, neuroimmunology, regulatory T cells, Th1, Th2
Transmitting editor: L. Steinman
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Chen, G. Han, J. Wang, R. Wang, R. Xu, B. Shen, J. Qian, and Y. Li Natural Killer Cells Modulate Overt Autoimmunity to Homeostasis in Nonobese Diabetic Mice after Anti-CD3 F(ab')2 Antibody Treatment through Secreting Transforming Growth Factor-{beta} Am. J. Pathol., September 1, 2009; 175(3): 1086 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wu, E. Center, G. Tsokos, and H. Weiner Suppression of murine SLE by oral anti-CD3: inducible CD4+CD25-LAP+ regulatory T cells control the expansion of IL-17+ follicular helper T cells Lupus, June 1, 2009; 18(7): 586 - 596. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Y. Wu, F. J. Quintana, and H. L. Weiner Nasal Anti-CD3 Antibody Ameliorates Lupus by Inducing an IL-10-Secreting CD4+CD25-LAP+ Regulatory T Cell and Is Associated with Down-Regulation of IL-17+CD4+ICOS+CXCR5+ Follicular Helper T Cells J. Immunol., November 1, 2008; 181(9): 6038 - 6050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Wasserman and B. D. Evavold Induction of Anergy by Antibody Blockade of TCR in Myelin Oligodendrocyte Glycoprotein-Specific Cells J. Immunol., June 1, 2008; 180(11): 7259 - 7264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, G. Han, J. Wang, R. Wang, R. Xu, B. Shen, J. Qian, and Y. Li Induction of Active Tolerance and Involvement of CD1d-Restricted Natural Killer T Cells in Anti-CD3 F(ab')2 Treatment-Reversed New-Onset Diabetes in Nonobese Diabetic Mice Am. J. Pathol., April 1, 2008; 172(4): 972 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chen, G. Han, J. Wang, R. Wang, R. Xu, B. Shen, J. Qian, and Y. Li Essential roles of TGF-{beta} in anti-CD3 antibody therapy: reversal of diabetes in nonobese diabetic mice independent of Foxp3+CD4+ regulatory T cells J. Leukoc. Biol., February 1, 2008; 83(2): 280 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ishikawa, H. Ochi, M.-L. Chen, D. Frenkel, R. Maron, and H. L. Weiner Inhibition of Autoimmune Diabetes by Oral Administration of Anti-CD3 Monoclonal Antibody Diabetes, August 1, 2007; 56(8): 2103 - 2109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Kohm, J. S. Williams, A. L. Bickford, J. S. McMahon, L. Chatenoud, J.-F. Bach, J. A. Bluestone, and S. D. Miller Treatment with Nonmitogenic Anti-CD3 Monoclonal Antibody Induces CD4+ T Cell Unresponsiveness and Functional Reversal of Established Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2005; 174(8): 4525 - 4534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Tran, S. J. Hodgkinson, N. Carter, M. Killingsworth, S. T. Spicer, and B. M. Hall Attenuation of Experimental Allergic Encephalomyelitis in Complement Component 6-Deficient Rats Is Associated with Reduced Complement C9 Deposition, P-Selectin Expression, and Cellular Infiltrate in Spinal Cords J. Immunol., May 1, 2002; 168(9): 4293 - 4300. [Abstract] [Full Text] [PDF]
|
|