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

Abstract

Because monoclonal antibodies (mAbs) directed against α4-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 α4β1/vcam-1-mediated interaction of autoaggressive T cells with the blood-brain barrier. A possible role for α4β7-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 α4, β7, the α4β7-heterodimer, and against VCAM- 1. Although encephalitogenic T cells express both α4-integrins, mabs directed against the α4β7-heterodimer or against the β7-subunit did not interfere with the development of EAE. In contrast, mabs directed against α4 and VCAM-1 inhibited or diminished clinical or histopathological signs of EAE. Our data demonstrate for the first time that α4β7 is not essential for the development of EAE. Furthermore, our in vitro studies suggest that the therapeutic effect of anti-α4-treatment of EAE might also be caused by inhibition of antigen-specific T cell proliferation.