CD4+ T cells require either B cells or CD8+ T cells to control spread and pathogenesis of a neurotropic infection

Immunity within the brain, specifically to virus-infected neurons, must be controlled to prevent neuron loss and impairment, though the process by which this occurs remains unclear. Here, we use a mouse model of neuron-restricted measles virus infection, in which immunocompetent adults survive challenge, whereas T and B cell-deficient mice succumb. This model allowed us to more precisely define the contributions of CD4+ T cells, CD8+ T cells, and B cells in neuroprotection. Both B cell knockout mice and mice depleted of CD8+ T cells survive challenge and show no signs of illness, though are less able to control viral replication than immunocompetent mice. In contrast, depletion of CD4+ T cells results in disease and death in all infected mice, though the kinetics of illness are delayed compared to RAG knockout mice. Our data suggest a coordinated interplay of adaptive immune components, which collectively controls viral spread and limits neuropathogenesis.