γ/δ T Cells in Multiple Sclerosis: Chemokine and Chemokine Receptor Expression

Abstract

γ/δ T cells are enriched in multiple sclerosis (MS) brain lesions and have been postulated to contribute to the pathogenesis of the disease. Increased expression of the chemokine receptors CCR5 and CXCR3 on T cells and raised amounts of the chemokines RANTES and IP-10 have been noted in the CSF and brain tissue of MS patients, but the contribution of γδ T cells to these increases is unknown. We therefore compared intracellular RANTES and IP-10 production as well as CCR5, CXCR3, and CXCR1 expression by γδ T cells derived from the blood and CSF of patients with MS and healthy controls (HC). We observed higher RANTES production by MS γδ than by αβ T cell lines. Most of the MS as well as the HC γδ and αβ T cell lines expressed CXCR3, while expression of CXCR1 was low. Interestingly, MS γδ T cell lines, compared to lines from HC, expressed lower levels of CCR5. Furthermore, CSF-derived γδ T cells had even lower CCR5 expression than blood-derived ones. The higher RANTES production by MS γδ T cell lines, together with a lower expression of CCR5, may reflect an autoregulatory loop, caused by an increased production of its ligands (RANTES, MIP-1α, and MIP-1β) or due to other pro-inflammatory cytokines. Alternatively, we show that lower CCR5 expression could also reflect the result of repeated in vivo stimulation of γδ T cells by autoantigens.