High dose antigen treatment with a peptide epitope of myelin basic protein modulates T cells in multiple sclerosis patients.

Abstract

One of the auto-antigens aberrantly targeted in Multiple sclerosis is myelin basic protein (MBP). In this study, chronic progressive multiple sclerosis (CPMS) patients receiving the experimental drug MBP8298, on a compassionate care trial, were examined before and after high dose peptide treatment for their circulating regulatory T-cell numbers and their responses to the common mitogens, phytohemagglutinin and poke-weed mitogen. Peripheral blood mononuclear cells (PBMCs) isolated from these patients before treatment displayed anergy upon stimulation with phytohemagglutinin; measured through reduced proliferation, IFN-γ and IL-17A secretion in an in vitro cell culture system. 6 Weeks and 6months after treatment their PBMCs displayed a reversal of anergy with phytohemagglutinin stimulation. There was also a marked increase in their CD4(+)CD25(+hi)FoxP3(+) T-cells regulatory T-cells. These results suggest that high dose MBP8298 treatment has a profound effect on the circulating T-cells of CPMS patients, capable of reversing peripheral anergy and establishing T regulation.

• Authors: Eric W Loo, Mark J Krantz, Babita Agrawal
• Journal: Cellular immunology (Cell Immunol) Vol. 280 Issue 1 Pg. 10-5 (Nov 2012) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 23246830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• IL17A protein, human
• IL2RA protein, human
• Interleukin-17
• Interleukin-2 Receptor alpha Subunit
• Myelin Basic Protein
• Peptide Fragments
• Transforming Growth Factor beta
• MBP-8298
• Interferon-gamma

Topics

• CD4 Lymphocyte Count
• Clonal Anergy (drug effects)
• Compassionate Use Trials
• Dose-Response Relationship, Immunologic
• Follow-Up Studies
• Humans
• Immunotherapy
• Interferon-gamma (blood)
• Interleukin-17 (blood)
• Interleukin-2 Receptor alpha Subunit (analysis)
• Multiple Sclerosis, Chronic Progressive (drug therapy, immunology, pathology)
• Myelin Basic Protein (administration & dosage, immunology, therapeutic use)
• Peptide Fragments (administration & dosage, immunology, therapeutic use)
• T-Lymphocytes, Regulatory (drug effects, immunology)
• Transforming Growth Factor beta (blood)
• Treatment Outcome