Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single Recombinant T-cell receptor ligand

Sushmita Sinha, Sandhya Subramanian, Lisa Miller, Thomas M. Proctor, Chris Roberts, Gregory G. Burrows, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Recombinant T-cell receptor ligands (RTLs) can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner, and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). Antigen specificity of RTL raises the question as to whether this treatment would be successful in MS patients where target antigens are unknown. Using spinal cord homogenate or combinations of two different peptides to induce disease, we found that treatment with single RTL could reverse EAE as long as targeted T-cells were present. Therapy with three different RTLs each caused a significant reduction in IL-17 and increases in IL-10 and IL-13 in peptide-activated splenocytes, reduced proliferation of both cognate and bystander specificities of lymph node cells, and reduced inflammatory lesions and secreted IL-17 and IL-2 from peptide-activated spinal cord cells. These results show that treatment with single RTLs can induce a cytokine switch in cognate T-cells that inhibits both the target and bystander T-cells, providing new evidence for the potential applicability of RTL therapy in MS.

Original languageEnglish (US)
Pages (from-to)3816-3823
Number of pages8
JournalJournal of Neuroscience
Volume29
Issue number12
DOIs
StatePublished - Mar 25 2009

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Bystander Effect
Autoimmune Experimental Encephalomyelitis
T-Cell Antigen Receptor
Autoimmunity
Cytokines
Ligands
Antigens
Multiple Sclerosis
Interleukin-17
T-Lymphocytes
Peptides
Spinal Cord
Therapeutics
Antigen Receptors
Interleukin-13
Interleukin-10
Interleukin-2
Lymph Nodes
Clinical Trials

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single Recombinant T-cell receptor ligand. / Sinha, Sushmita; Subramanian, Sandhya; Miller, Lisa; Proctor, Thomas M.; Roberts, Chris; Burrows, Gregory G.; Vandenbark, Arthur; Offner, Halina.

In: Journal of Neuroscience, Vol. 29, No. 12, 25.03.2009, p. 3816-3823.

Research output: Contribution to journalArticle

Sinha, Sushmita ; Subramanian, Sandhya ; Miller, Lisa ; Proctor, Thomas M. ; Roberts, Chris ; Burrows, Gregory G. ; Vandenbark, Arthur ; Offner, Halina. / Cytokine switch and bystander suppression of autoimmune responses to multiple antigens in experimental autoimmune encephalomyelitis by a single Recombinant T-cell receptor ligand. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 12. pp. 3816-3823.
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