CTLA-4-Fc treatment of ongoing EAE improves recovery, but has no effect upon relapse rate. Implications for the mechanisms involved in disease perpetuation

Several laboratories including ours have shown that T cell co-stimulation m ediated through B7-1 or B7-2 is critical to the initiation of EAE. The role of T cell co-stimulation in ongoing EAE is less clear. In the present stud y, 33- mice with established EAE were randomly assigned to receive treatmen t with either CTLA-4-Fc or control Ig. Mice were followed daily by clinical scoring for 2 months post-immunization. A significant improvement in the d egree of recovery following the acute episode and following relapses of EAE was observed in those mice randomized to CTLA-4-Fc treatment. Full clinica l remission occurred twice as often in the CTLA-4-Fc group as in those mice receiving placebo, whereas placebo-treated mice were more likely to develo p a stable prolonged neurologic deficit. Serial clinical scoring revealed n o effect of CTLA-4-Fc upon relapse rate, with greater than 80% of the mice in each group displaying at least one clinical EAE relapse. In that the act ivation of memory T cells is relatively independent of T cell co-stimulatio n, these results indicate that development of chronic disease is associated with the activation of naive T cells and the recruitment of the latter cel ls into the disease process. Blocking B7 molecules may be beneficial in the treatment of established CNS inflammatory demyelinating diseases such as m ultiple sclerosis. (C) 1999 Elsevier Science B.V. All rights reserved.