Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-α-induced oligodendrocyte apoptosis

Abstract

In multiple sclerosis (MS), damage to oligodendrocytes is believed to be caused by an aberrant immune response initiated by autoreactive Tcells. Increasing evidence indicates that these Tcells are not exclusively detrimental but might also exert protective effects. We report for the first time that myelin-reactive T-cell clones from eight MS patients (6/19) and five healthy controls (4/11) produce leukemia inhibitory factor (LIF), a member of the neuropoietic family of neurotrophins. In addition, T-cell clones specific for tetanus toxoid, CD4[+] and CD8[+] T cells, and monocytes, but not B cells, secreted LIF. LIF-producing T lymphocytes and macrophages were also identified immunohistochemically in both active and chronic-active MS lesions. We further demonstrated dose-dependent protective effects of LIF on tumor necrosis factor-α-induced apoptosis of oligodendrocytes. In conclusion, our data demonstrate that peripheral and CNS-infiltrating T cells from MS patients produce LIF, a protective factor for oligodendrocytes. This study emphasizes that secretion of LIF may contribute to the neuroprotective effects of autoreactive T cells.