Long-term therapy with glatiramer acetate in multiple sclerosis: effect onT-cells

Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and effect T-cells that ore specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patie nts and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-beta therapy on the in vitro prolife ration of GA-responsive T-cells of MS patients. We found that GA induces th e proliferation of T-cells isolated from individuals who have not been prev iously exposed to GA, and that long-term in vivo therapy of MS patients wit h GA abrogates the GA-induced proliferative response of T-cells. In GA-trea ted patients, there is no evidence of generalized immunosuppression; both t etanus toroid and anti-CD3 induced proliferative responses remain unaffecte d We Propose that prolonged in vivo exposure to GA may result in the eventu al induction of energy or deletion of a population of GA-responsive cells t hat may also be T-cells that ore pathogenic in MS. This mechanism of action , in addition to other mechanisms that have been demonstrated, suggests tha t GA has pleiotropic effects on the immune system in MS.