Access of protective antiviral antibody to neuronal tissues requires CD4 T cell help

Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunopriviledged tissues such as the brain and the peripheral nervous system, are shielded from plasma proteins, by the blood-brain barrier(1) and blood nerve barrier(2), respectively. Yet, circulating antibodies must somehow gain access to these tissues in order to mediate their antimicrobial functions. Here, we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host following immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia (DRG) and spinal cord in response to HSV-2 infection. Once inside these neuronal tissues, CD4 T cells secrete interferon (IFN)-γ and mediate local increase in vascular permeability, enabling antibody access for viral control. A similar requirement for CD4 T cells for antibody access to the brain was observed following intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 help in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread.