Since CD4+ T cells are essential for activation of CD8+ T cells and for their arrest in the brain during ECM [40], effective regulation of CD4+ T cells by CTLA-4 is likely to interrupt the chain of events leading to ECM at a much earlier stage of infection than is regulation of CD8+ T cell activity (by either CTLA-4 or PD-1/PD-L1). Here, PDCD1 is linked to infection.