Increased numbers of mononuclear cells from blood and CSF expressing interferon-gamma mRNA in multiple sclerosis are from both the CD4+and the CD8+subsets

Activated, cytokine-producing lymphocytes may regulate central nervous syst em (CNS) inflammation in multiple sclerosis (MS). We utilize a novel combin ation of in situ hybridization (ISH) and immunocytochemical staining of per ipheral blood lymphocytes (PBLs) to identify spontaneously interferon-gamma (IFN gamma) mRNA expressing cells as CD4+ or CD8+. A major proportion of t he IFN gamma mRNA expressing lymphocytes belonged to the CD4+ lineage, whic h concords with the cellular composition of MS brain lesions, findings in e xperimental models and the HLA class II haplotype association in MS. Then w ere also significantly more CD8+ IFN gamma mRNA expressing lymphocytes in t he MS patients compared with healthy controls, further suggesting the contr ibution of activated cells from this lineage in the inflammatory response i n MS. Both CD4+ and CD8+ IFN gamma mRNA expressing cells were enriched in t he cerebrospinal fluid (CSF) as compared with the peripheral blood of the M S patients. Combined with emerging genetic data on HLA class I influences, our data argues for a joint role of activated CD8+ and CD4+ cells in the pa thogenesis of MS.