Increased expression of B7-1 costimulatory molecule on cerebrospinal fluid cells of patients with multiple sclerosis and infectious central nervous system disease

Abstract

The expression of the costimulatory molecule B7-1 (BB-1; CD80) and its ligand CD28 was investigated on peripheral blood (PB) and cerebrospinal fluid (CSF) T and B lymphocytes and monocytes in 11 patients with relapsing-remitting multiple sclerosis (MS), 21 age-matched healthy controls and 10 patients with central nervous system (CNS) infectious disease (CID). Three channel flow cytometry was used with a novel gating technique in order to unambiguously identify the low numbers of B lymphocytes present in normal CSF. There was a significantly higher fraction of B7-1 + B lymphocytes in the CSF of patients with MS (72%) and CID (69%) when compared with healthy individuals (53%; p<0.0001 and p<0.002, respectively). Furthermore, two patients with a clinical picture of encephalitis showed a profoundly increased B7-1 expression on CSF monocytes. Comparison of absolute numbers of B7-1 + B lymphocytes/mL CSF between MS patients and healthy controls revealed a highly increased frequency of these cells among MS patients (235 cells/mL in MS patients versus 3.9 cells/mL in controls; p<0.0001) with no overlap between the groups, which was otherwise seen for all other analyzed cell populations. We therefore hypothesize that activated B lymphocytes expressing high levels of B7-1 may be of pathogenetic importance in the development and maintenance of the MS disease.