CX(3)CR1 drives cytotoxic CD4(+)CD28(-) T cells into the brain of multiple sclerosis patients

Bieke Broux, Kim Pannemans, Xin Zhang, Silva Markovic-Plese, Tom Broekmans, Bert O. Eijnde, Bart Van Wijmeersch, Veerle Somers, Piet Geusens, Susanne van der Pol, Jack van Horssen, Piet Stinissen, Niels Hellings*

*Corresponding author for this work

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79 Citations (Web of Science)


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.
Original languageEnglish
Pages (from-to)10-19
JournalJournal of Autoimmunity
Issue number1
Publication statusPublished - Feb 2012


  • Multiple sclerosis
  • T cells
  • Immunosenescence
  • Fractalkine
  • CX(3)CR1

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