Journal of Neuroimmunology
Volume 225, Issue 1 , Pages 52-61 , 25 August 2010

Binding of recombinant T cell receptor ligands (RTL) to antigen presenting cells prevents upregulation of CD11b and inhibits T cell activation and transfer of experimental autoimmune encephalomyelitis

  • Sushmita Sinha

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States
    • ,
  • Lisa Miller

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • ,
  • Sandhya Subramanian

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • ,
  • Owen J.T. McCarty

      Affiliations

    • Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, United States
    • ,
  • Thomas Proctor

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • Tykeson MS Research Laboratory, Oregon Health & Science University, Portland, OR 97239, United States
    • ,
  • Roberto Meza-Romero

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States
    • Tykeson MS Research Laboratory, Oregon Health & Science University, Portland, OR 97239, United States
    • ,
  • Jianya Huan

      Affiliations

    • Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States
    • Tykeson MS Research Laboratory, Oregon Health & Science University, Portland, OR 97239, United States
    • ,
  • Gregory G. Burrows

      Affiliations

    • Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States
    • Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, United States
    • Tykeson MS Research Laboratory, Oregon Health & Science University, Portland, OR 97239, United States
    • ,
  • Arthur A. Vandenbark

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States
    • Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, United States
    • Tykeson MS Research Laboratory, Oregon Health & Science University, Portland, OR 97239, United States
    • Contributed equally to this work.
    • ,
  • Halina Offner

      Affiliations

    • Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States
    • Department of Neurology, Oregon Health & Science University, Portland, OR 97239, United States
    • Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, United States
    • Tykeson MS Research Laboratory, Oregon Health & Science University, Portland, OR 97239, United States
    • Corresponding Author InformationCorresponding author. Neuroimmunology Research R&D-31, Portland V.A. Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR 97239, United States. Tel.: +1 503 721 7893; fax: +1 503 721 7975.
    • Contributed equally to this work.

Received 11 March 2010 ,Revised 19 April 2010 ,Accepted 21 April 2010.

References 

  1. Bauer J, Huitinga I, Zhao W, Lassmann H, Hickey WF, Dijkstra CD. The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis. Glia. 1995;15:437–446
  2. Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J. Mol. Med. 1997;75:165–173
  3. Bullard DC, Hu X, Schoeb TR, Axtell RC, Raman C, Barnum SR. Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis. J. Immunol. 2005;175:6327–6333
  4. Burrows GG, Bebo BF, Adlard KL, Vandenbark AA, Offner H. Two-domain MHC class II molecules form stable complexes with myelin basic protein 69–89 peptide that detect and inhibit rat encephalitogenic T cells and treat experimental autoimmune encephalomyelitis. J. Immunol. 1998;161:5987–5996
  5. Burrows GG, Chang JW, Bachinger HP, Bourdette DN, Offner H, Vandenbark AA. Design, engineering and production of functional single-chain T cell receptor ligands. Protein Eng. 1999;12:771–778
  6. Burrows GG, Chou YK, Wang C, Chang JW, Finn TP, Culbertson NE, et al. Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells. J. Immunol. 2001;167:4386–4395
  7. Chou YK, Culbertson N, Rich C, LaTocha D, Buenafe AC, Huan J, et al. T-cell hybridoma specific for myelin oligodendrocyte glycoprotein-35-55 peptide produced from HLA-DRB1*1501-transgenic mice. J. Neurosci. Res. 2004;77:670–680
  8. Davis MM, Boniface JJ, Reich Z, Lyons D, Hampl J, Arden B, et al. Ligand recognition by alpha beta T cell receptors. Annu. Rev. Immunol. 1998;16:523–544
  9. Gordon EJ, Myers KJ, Dougherty JP, Rosen H, Ron Y. Both anti-CD11a (LFA-1) and anti-CD11b (MAC-1) therapy delay the onset and diminish the severity of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 1995;62:153–160
  10. Huan J, Subramanian S, Jones R, Rich C, Link J, Mooney J, et al. Monomeric recombinant TCR ligand reduces relapse rate and severity of experimental autoimmune encephalomyelitis in SJL/J mice through cytokine switch. J. Immunol. 2004;172:4556–4566
  11. Link J. Partial MHC class II molecules preferentially bind to B cells. J. Immunol. 2007;78:
  12. Link JM, Rich CM, Korat M, Burrows GG, Offner H, Vandenbark AA. Monomeric DR2/MOG-35-55 recombinant TCR ligand treats relapses of experimental encephalomyelitis in DR2 transgenic mice. Clin. Immunol. 2007;123:95–104
  13. Nicholson GC, Tennant RC, Carpenter DC, Sarau HM, Kon OM, Barnes PJ, et al. A novel flow cytometric assay of human whole blood neutrophil and monocyte CD11b levels: upregulation by chemokines is related to receptor expression, comparison with neutrophil shape change, and effects of a chemokine receptor (CXCR2) antagonist. Pulm. Pharmacol. Ther. 2007;20:52–59
  14. Offner H, Subramanian S, Wang C, Afentoulis M, Vandenbark AA, Huan J, et al. Treatment of passive experimental autoimmune encephalomyelitis in SJL mice with a recombinant TCR ligand induces IL-13 and prevents axonal injury. J. Immunol. 2005;175:4103–4111
  15. Offner H, Sinha S, Wang C, Burrows GG, Vandenbark AA. Recombinant T cell receptor ligands: immunomodulatory, neuroprotective and neuroregenerative effects suggest application as therapy for multiple sclerosis. Rev. Neurosci. 2008;19:327–339
  16. Rubel C, Miliani De Marval P, Vermeulen M, Isturiz MA, Palermo MS. Lipopolysaccharide enhances FcgammaR-dependent functions in vivo through CD11b/CD18 up-regulation. Immunology. 1999;97:429–437
  17. Sinha S, Subramanian S, Proctor TM, Kaler LJ, Grafe M, Dahan R, et al. A promising therapeutic approach for multiple sclerosis: recombinant T-cell receptor ligands modulate experimental autoimmune encephalomyelitis by reducing interleukin-17 production and inhibiting migration of encephalitogenic cells into the CNS. J. Neurosci. 2007;27:12531–12539
  18. Sinha S, Subramanian S, Miller L, Proctor TM, Roberts C, Burrows GG, et al. Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single recombinant T-cell receptor ligand. J. Neurosci. 2009;29:3816–3823
  19. Sinha S, Subramanian S, Emerson-Webber A, Lindner M, Burrows GG, Grafe M, et al. Recombinant TCR ligand reverses clinical signs and CNS damage of EAE induced by recombinant human MOG. J. Neuroimmune. Pharmacol. 2010;5:231–240
  20. Vandenbark AA, Rich C, Mooney J, Zamora A, Wang C, Huan J, et al. Recombinant TCR ligand induces tolerance to myelin oligodendrocyte glycoprotein 35–55 peptide and reverses clinical and histological signs of chronic experimental autoimmune encephalomyelitis in HLA-DR2 transgenic mice. J. Immunol. 2003;171:127–133
  21. Wang C, Mooney JL, Meza-Romero R, Chou YK, Huan J, Vandenbark AA, et al. Recombinant TCR ligand induces early TCR signaling and a unique pattern of downstream activation. J. Immunol. 2003;171:1934–1940
  22. Wang C, Gold BG, Kaler LJ, Yu X, Afentoulis ME, Burrows GG, et al. Antigen-specific therapy promotes repair of myelin and axonal damage in established EAE. J. Neurochem. 2006;98:1817–1827
  23. Yadav V, Bourdette D, Bowen JD, Lynch SG, Mattson D, Preinigerova J, et al. Recombinant T cell receptor ligand (RTL) for the treatment of multiple sclerosis: report of a phase I clinical trial. Neurology. 2010;74(S2):A293–A294

PII: S0165-5728(10)00173-6

doi: 10.1016/j.jneuroim.2010.04.013

Journal of Neuroimmunology
Volume 225, Issue 1 , Pages 52-61 , 25 August 2010

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