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Leukemia inhibitory factor is produced by myelin‐reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor‐α‐induced oligodendrocyte apoptosis
Author(s) -
Vanderlocht Joris,
Hellings Niels,
Hendriks Jerome J.A.,
Vandenabeele Frank,
Moreels Marjan,
Buntinx Mieke,
Hoekstra Dick,
Antel Jack P.,
Stinissen Piet
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20781
Subject(s) - leukemia inhibitory factor , oligodendrocyte , immunology , multiple sclerosis , tumor necrosis factor alpha , myelin , apoptosis , t cell , biology , cd8 , cancer research , cytotoxic t cell , immune system , inflammation , endocrinology , central nervous system , in vitro , biochemistry , interleukin 6
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‐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. © 2006 Wiley‐Liss, Inc.