Abstract
We investigated the role of the CD134 (also named OX40) molecule in experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS). We examined the susceptibility of Cd134(-/-) mice to EAE, an autoimmune murine model that is dependent on infiltrating CD4+ T lymphocytes reactive to myelin proteins. EAE induced by myelin oligodendrocyte glycoprotein (MOG) injection in Cd134(-/-) mice showed less severe clinical signs of disease and markedly reduced inflammatory infiltrates within the central nervous system (CNS). Resistance was associated with a strong reduction of pathogenic IFNgamma-producing T cells infiltrating the CNS of Cd134(-/-) mice. Furthermore, analysis of CNS tissue sections from EAE animals and MS patients revealed the presence of CD134+ cells that were localized in active lesions, mainly in perivascular infiltrates. The presence of CD134-expressing T cells in brain tissue of MS patients and EAE affected mice, together with the functional evidence provided by the significant decrease in disease score obtained in Cd134(-/-) mice, indicate that interfering with the CD134 molecule in T cells may be an appropriate target for therapeutic intervention in active MS.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Brain / immunology*
-
Brain / metabolism*
-
Brain / pathology
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / pathology
-
Cell Division / genetics
-
Cell Division / immunology
-
Cell Movement / genetics
-
Cell Movement / immunology
-
Down-Regulation / genetics
-
Down-Regulation / immunology
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Encephalomyelitis, Autoimmune, Experimental / immunology*
-
Female
-
Humans
-
Interferon-gamma / antagonists & inhibitors
-
Interferon-gamma / biosynthesis
-
Lymphocyte Activation / genetics
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Molecular Sequence Data
-
Multiple Sclerosis / immunology*
-
Multiple Sclerosis / pathology
-
Myelin Sheath / pathology
-
Receptors, OX40
-
Receptors, Tumor Necrosis Factor / biosynthesis
-
Receptors, Tumor Necrosis Factor / deficiency
-
Receptors, Tumor Necrosis Factor / genetics
-
Receptors, Tumor Necrosis Factor / physiology*
-
Spinal Cord / immunology*
-
Spinal Cord / metabolism*
-
Spinal Cord / pathology
-
T-Lymphocyte Subsets / immunology
-
T-Lymphocyte Subsets / pathology
-
Th1 Cells / immunology
-
Th1 Cells / metabolism
-
Th1 Cells / pathology
-
Up-Regulation / genetics
-
Up-Regulation / immunology*
Substances
-
Receptors, OX40
-
Receptors, Tumor Necrosis Factor
-
TNFRSF4 protein, human
-
Tnfrsf4 protein, mouse
-
Interferon-gamma