CX3CR1 drives cytotoxic CD4+ CD28− T cells into the brain of multiple sclerosis patients

B Broux, K Pannemans, X Zhang… - Journal of …, 2012 - Elsevier
B Broux, K Pannemans, X Zhang, S Markovic-Plese, T Broekmans, BO Eijnde…
Journal of autoimmunity, 2012Elsevier
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+ …
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 CX3CR1, the fractalkine receptor, as a selective marker to discriminate CD4+CD28 T cells from their CD4+CD28+ counterparts. CX3CR1 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.
Elsevier