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; received in revised form 19 April 2010; accepted 21 April 2010. published online 24 May 2010.

Abstract 

Recombinant T cell ligands (RTLs) ameliorate experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner. We evaluated effects of RTL401 (I-As α1β1+PLP-139-151) on splenocytes from SJL/J mice with EAE to study RTL-T cell tolerance-inducing mechanisms. RTLs bound to B, macrophages and DCs, through RTL-MHC-α1β1 moiety. RTL binding reduced CD11b expression on splenic macrophages/DC, and RTL401-conditioned macrophages/DC, not B cells, inhibited T cell activation. Reduced ability of RTL- incubated splenocytes to transfer EAE was likely mediated through macrophages/DC, since B cells were unnecessary for RTL treatment of EAE. These results demonstrate a novel pathway of T cell regulation by RTL-bound APCs.

Keywords: EAE, RTLs, Tolerance, APCs

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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