J Neuroimmunol. 2003 Dec;145(1-2):1-11
Carboni S, Aboul-Enein F, Waltzinger C, Killeen N, Lassmann H, Pena-Rossi
C.
Serono Pharmaceutical Research Institute, 14, Chemin Aulx, 1228 Plan-les
Ouates, Switzerland
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.