Document Server@UHasselt >
Research >
Research publications >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2346

Title: Functional properties of myelin oligodendrocyte glycoprotein-reactive T cells in multiple sclerosis patients and controls
Authors: VAN DER AA, Annegret
Bernard, C.C.A.
Issue Date: 2003
Citation: JOURNAL OF NEUROIMMUNOLOGY, 137(1-2). p. 164-176
Abstract: Autoimmune T-cell reactivity to myelin components may be implicated in the initiation or maintenance of the inflammation leading to myelin destruction in multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG), a quantitatively minor myelin protein, is an important candidate autoantigen in MS. We studied T-cell responses to recombinant MOG (extracellular domain, rMOG) and a panel of four peptides within this domain (amino acids 1-22, 34-56, 64-86 and 74-96) in MS patients and healthy controls (NS). Frequency analysis of T cells reactive to rMOG as measured by IFN-gamma ELISPOT did not reveal significant differences between MS patients and controls. MOG-reactive T-cell lines and clones (TCL/TCC) were generated by stimulating PBMC of four MS patients and three healthy subjects with a cocktail of the four MOG peptides. The functional properties of 50 MOG peptide-reactive TCL/TCC obtained were studied. All TCL were TCRalphabeta + CD4+ and 20 TCL showed reactivity to MOG peptides 1-22, 13 to 34-56, 1 to 64-86 and 16 to 74-96. No significant differences in peptide recognition Were observed between MS patients and controls. The T-cell receptor (TCR) hypervariable regions of MOG-reactive TCL/TCC showed a heterogeneous usage of various TCR V(-D)-J elements. The data provide no evidence for clonal expansions within the MOG-reactive T-cell repertoire of the two study groups. Intracellular cytokine analysis demonstrated predominantly Th1-TCC (IFN-gamma+/IL-4 -) in MS patients, while most MOG-reactive TCC of control subjects had a mixed Th0/Th1 phenotype. Furthermore, the MS-derived MOG-reactive TCC produced increased levels of TNF-alpha upon antigen stimulation as compared to controls. Most of the MS-derived MOG-TCC induced specific cytolysis of autologous MOG-pulsed PBMC (9/11) while none of the MOG-TCC isolated from control subjects showed this cytotoxicity (0/8). In conclusion, although the frequency of anti-MOG T cells was similar in MS patients and controls, our data indicate potential differences in the functional properties of MOG TCL in MS patients versus healthy controls which may relate to their role in the disease process. (C) 2003 Elsevier Science B.V. All rights reserved.
Notes: Limburgs Univ Ctr, Biomed Onderzoek Inst BIOMED DW1, Autoimmune Dis Unit, B-3590 Diepenbeek, Belgium. Transnatl Univ Limburg, Sch Life Sci, Diepenbeek, Belgium. La Trobe Univ, Neuroimmunol Lab, Bundoora, Vic, Australia.Stinissen, P, Limburgs Univ Ctr, Biomed Onderzoek Inst BIOMED DW1, Autoimmune Dis Unit, Univ Campus Bldg A, B-3590 Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/2346
DOI: 10.1016/S0165-5728(03)00048-1
ISI #: 000182443700020
ISSN: 0165-5728
Category: A1
Type: Journal Contribution
Validation: ecoom, 2004
Appears in Collections: Research publications

Files in This Item:

There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.