Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-alpha-induced oligodendrocyte apoptosis.
In multiple sclerosis (MS), damage to oligodendrocytes is believed to be caused by an aberrant immune response initiated by autoreactive T cells. Increasing evidence indicates that these T cells 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-alpha-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.
Vanderlocht
Joris
J
Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Hasselt University, Diepenbeek, Belgium.
Hellings
Niels
N
Hendriks
Jerome J A
JJ
Vandenabeele
Frank
F
Moreels
Marjan
M
Buntinx
Mieke
M
Hoekstra
Dick
D
Antel
Jack P
JP
Stinissen
Piet
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020934:Ciliary Neurotrophic Factor / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology; D009186:Myelin Sheath / Q000276:immunology*; D009836:Oligodendroglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D014409:Tumor Necrosis Factor-alpha