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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 OP 'T EIJNDE, Bert 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 | Source: | 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. | Keywords: | Multiple sclerosis;T cells;Immunosenescence;Fractalkine;CX(3)CR1 | Document URI: | http://hdl.handle.net/1942/13595 | ISSN: | 0896-8411 | e-ISSN: | 1095-9157 | DOI: | 10.1016/j.jaut.2011.11.006 | ISI #: | 000301313400002 | Rights: | 2011 Elsevier Ltd. All rights reserved. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2013 |
Appears in Collections: | Research publications |
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