Superantigen Reactivity of γδ T Cell Clones Isolated from Patients with Multiple Sclerosis and Controls

Abstract

γδ T cells have been implicated as playing a role in the demyelinating processes of multiple sclerosis (MS). However, the nature of the ligands which lead to activation and accumulation of γδ T cells in the brain lesions remains unknown. This study was undertaken to examine whether γδ T cells derived from cerebrospinal fluid and blood of MS patients could be stimulated by bacterial superantigens: staphylococcal enterotoxins A and B and toxic shock syndrome toxin-1. A panel of 16 γδ T cell clones isolated from MS patients and controls was found to react with the superantigens used at a nanogram range and displayed specific cytotoxic activity toward target cells pulsed with the corresponding superantigens. The responses of the γδ T cell clones did not require MHC-matched accessory cells and were not blocked by antibodies to the MHC molecules, suggesting a non-MHC restricted interaction. The superantigen reactivity was associated with both Vδ2+/Vγ2+and Vδ1+/Vγ1+subsets, reportedly found in the MS lesions. Our data suggest an alternative pathway which may account for γδ T cell activation in MS.