title: Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help.
abstract: Circulating antibodies can access most tissues to mediate surveillance and elimination of invading pathogens. Immunoprivileged tissues such as the brain and the peripheral nervous system are shielded from plasma proteins by the blood-brain barrier and blood-nerve barrier, respectively. Yet, circulating antibodies must somehow gain access to these tissues to mediate their antimicrobial functions. Here we examine the mechanism by which antibodies gain access to neuronal tissues to control infection. Using a mouse model of genital herpes infection, we demonstrate that both antibodies and CD4 T cells are required to protect the host after immunization at a distal site. We show that memory CD4 T cells migrate to the dorsal root ganglia and spinal cord in response to infection with herpes simplex virus type 2. Once inside these neuronal tissues, CD4 T cells secrete interferon-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 is observed after intranasal challenge with vesicular stomatitis virus. Our results reveal a previously unappreciated role of CD4 T cells in mobilizing antibodies to the peripheral sites of infection where they help to limit viral spread.
authors.affiliation: Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Iijima
authors.affiliation: Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.|Howard Hughes Medical Institute, Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002199:Capillary Permeability / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000276:immunology; D006558:Herpes Genitalis / Q000276:immunology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D007156:Immunologic Memory / Q000276:immunology; D039441:Integrin alpha4 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009417:Nerve Tissue / Q000276:immunology; D009420:Nervous System / Q000276:immunology*; D009474:Neurons / Q000276:immunology; D009666:Nose / Q000821:virology; D011961:Receptors, Fc; D013116:Spinal Cord / Q000276:immunology; D018116:Vesiculovirus / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D039441:Integrin alpha4; D007371:Interferon-gamma; C100688:Fc receptor, neonatal