The development of experimental autoimmune encephalomyelitis in the mouse requires α4-integrin but not α4β7-integrin

Because monoclonal antibodies (mAbs) directed against alpha 4-integrin and VCAM-1 inhibit the development of experimental autoimmune encephalomyelitis (EAE) in vivo, it has been concluded that the successful therapeutic effect is due to interference with alpha 4 beta 1/VCAM-1-mediated interaction of autoaggressive T cells with the blood-brain barrier. A possible role for alpha 4 beta 7-integrin, or interference with other T cell mediated events during the pathogenesis of EAE, has not been considered. We have compared the effects of mAb therapy on the development of EAE in the SJL/N mouse, using a large panel of mAbs directed against alpha 4, beta 7, the alpha 4 beta 7-heterodimer, and against VCAM-1. Although encephalitogenic T cells express both alpha 4-integrins, mAbs directed against the alpha 4 beta 7-heterodimer or against the beta 7-subunit did not interfere with the development of EAE. In contrast, mAbs directed against alpha 4 and VCAM-1 inhibited or diminished clinical or histopathological signs of EAE, Our data demonstrate for the first time that alpha 4 beta 7 is not essential for the development of EAE. Furthermore, our in vitro studies suggest that the therapeutic effect of anti-alpha 4-treatment of EAE might also be caused by inhibition of antigen-specific T cell proliferation.