CD25 regulatory T cells determine secondary but not primary remission in EAE: impact on long-term disease progression.

Multiple sclerosis (MS) is often characterized by several relapses and remissions during long-term disease, but neither the responsible cells nor the mechanisms are known to date. Using an animal model of multiple sclerosis, relapsing experimental autoimmune encephalomyelitis (R-EAE) CD4+CD25+ Treg cells expressing Foxp3 and CTLA-4 intracellularly and T lymphocytes expressing surface CTLA-4 were identified in the CNS. The first remission occurred even after depletion of Treg cells, but secondary remissions from EAE were ablated. Despite the unaltered first remission autoantigen rechallenge revealed already an amplified cytokine response during acute phase. These results indicate that the cellular composition during first attack of MS predicts long-term disease progression.