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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/13595

Title: CX(3)CR1 drives cytotoxic CD4(+)CD28(-) T cells into the brain of multiple sclerosis patients
Authors: Broux, Bieke
Pannemans, Kim
Zhang, Xin
Markovic-Plese, Silva
Broekmans, Tom
Eijnde, Bert O.
Van Wijmeersch, Bart
Somers, Veerle
Geusens, Piet
van der Pol, Susanne
van Horssen, Jack
Stinissen, Piet
Hellings, Niels
Issue Date: 2012
Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation: JOURNAL OF AUTOIMMUNITY, 38 (1), p. 10-19
Abstract: Immunosenescence, or ageing of the immune system, contributes to the increased morbidity and mortality seen in the elderly population. Premature immunosenescence is shown to occur in a subgroup of patients with autoimmune diseases. One of the main characteristics of immunosenescence is the expansion of CD4(+)CD28(-) T cells in the blood. In this study, we investigate the potential contribution of these cells to disease processes in a subgroup of multiple sclerosis (MS) and rheumatoid arthritis (RA) patients. Characterization of CD4(+)CD28(-) T cells in patients and healthy controls reveals that they have an inflammation-seeking effector-memory T cell phenotype with cytotoxic properties, as they expel cytotoxic granules in response to a polyclonal stimulus or MS-related autoantigens. We identify CX(3)CR1, the fractalkine receptor, as a selective marker to discriminate CD4(+)CD28(-) T cells from their CD4(+)CD28(+) counterparts. CX(3)CR1 expression enables CD4(+)CD28(-) T cells to migrate towards a fractalkine gradient in vitro. In addition, we find increased levels of fractalkine in the cerebrospinal fluid and inflammatory lesions of MS patients. We demonstrate for the first time that CD4(+)CD28(-) T cells accumulate in MS lesions of a subgroup of patients. Moreover, we have indications that these cells are cytotoxic in the target tissue. Overall, our findings suggest that CD4(+)CD28(-) T cells migrate in response to a chemotactic gradient of fractalkine to sites of inflammation, where they contribute to the inflammatory processes in a subgroup of patients with MS and RA. (C) 2011 Elsevier Ltd. All rights reserved.
Notes: [Broux, Bieke; Pannemans, Kim; Broekmans, Tom; Eijnde, Bert O.; Van Wijmeersch, Bart; Somers, Veerle; Geusens, Piet; Stinissen, Piet; Hellings, Niels] Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. [Broux, Bieke; Pannemans, Kim; Broekmans, Tom; Eijnde, Bert O.; Van Wijmeersch, Bart; Somers, Veerle; Geusens, Piet; Stinissen, Piet; Hellings, Niels] Transnat Univ Limburg, Sch Life Sci, B-3590 Diepenbeek, Belgium. [Zhang, Xin; Markovic-Plese, Silva] Univ N Carolina, Dept Neurol, Chapel Hill, NC 27514 USA. [Markovic-Plese, Silva] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27514 USA. [Broekmans, Tom; Eijnde, Bert O.; Van Wijmeersch, Bart] PHL Univ Coll, REVAL Rehabil Res Ctr, Dpt Healthcare, B-3590 Diepenbeek, Belgium. [Van Wijmeersch, Bart] Mariaziekenhuis Noord Limburg, B-3900 Overpelt, Belgium. [Van Wijmeersch, Bart] Revalidatie & MS Ctr, B-3900 Overpelt, Belgium. [Geusens, Piet] Maastricht Univ Med Ctr, Dept Internal Med Rheumatol, NL-6229 HX Maastricht, Netherlands. [van der Pol, Susanne; van Horssen, Jack] Vrije Univ Amsterdam Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 BT Amsterdam, Netherlands. [van Horssen, Jack] Vrije Univ Amsterdam Med Ctr, Dept Neuropathol, NL-1081 BT Amsterdam, Netherlands.
URI: http://hdl.handle.net/1942/13595
DOI: 10.1016/j.jaut.2011.11.006
ISI #: 000301313400002
ISSN: 0896-8411
Category: A1
Type: Journal Contribution
Validation: ecoom, 2013
Appears in Collections: Research publications

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