Measles virus-polypeptide specificity of the cytotoxic T-lymphocyte response in multiple sclerosis

Some patients with multiple sclerosis (MS) have been shown previously to have a reduced capacity to generate measles virus (MV)-specific cytotoxic T-lymphocytes (CTLs). The mechanism of this reduction is not understood. Possiblities include sequestration of MV-CTLs within the central nervous system (CNS), abnormalities in regulation of this response (e.g., suppression), a defect in the T-cell repertoire of MS patients and a defect in the induction or maintenance of the CTL response to MV. To examine these possibilities, the CTL response to three purified polypeptides of MV (hemagglutinin (HA), fusion (F), and nucleocapsid (NC)) was studied in eight helathy controls and 14 patients with multiple sclerosis. A defect in the response to two polypeptides of the virus (HA and NC) was found in the MS patients with reduced MV-CTL response. The response to F was also reduced but to a lesser extent. Limiting dilution analysis of the MV polypeptide-specific CTL response indicated that suppression is an unlikely cause for the reduction in CTL activity. The lymphoproliferative response to MV, HA, F, and NC was comparable in three MS patients and three controls examined. Together, the results of these studies indicate that the reduced MV-CTL response in MS patients was not due to a defect in the T-cell repertoire or sequestration due to cross-reactivity with a single myelin antigen. More likely mechanism include abnormalities in the induction or maintenance of the MV-CTL response or sequestration within theCNS due to recognition of MV antigens.