Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell clones from patients with multiple sclerosis

T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their ability to produce interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interleukin-4 (IL-4). The CSF-T clones were compared for their ability to produce cytokines with autologous peripheral T clones and with liver-infiltrating T cell clones from patients with chronic active hepatitis. IL-4 production was also compared with that by peripheral T clones derived from atopic patients. All the CSF-T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha. These cytokines were synthesized in significantly larger amounts by CSF T clones than by reference clones. Moreover, they were capable of secreting IL-2, but not IL-4. We conclude that the CSF-CD4+ T clones could constitute a subset with functional properties similar to those of T helper 1 (Th1)inflammatory cells of the mouse; and that the large amounts of TNF produced by CSF T cell clones strongly suggest a significant role for this cytokine in MS immunopathogenesis.