Antibodies are required for full protection against neurotrophic viruses, but how antibodies gain access to neuronal tissues is unclear. In Nature, Iijima and Iwasaki show that antigen-specific CD4+ memory T cells (Tmem cells) facilitate the entry of IgG2 antibodies into the dorsal root ganglia during infection with herpes simplex virus type 2 and their entry into other neuronal sites after infection with vesicular stomatitis virus. Circulating antibodies to herpes simplex virus type 2 provide protection in the innervating neurons but not in vaginal tissues. Local production of interferon-γ (IFN-γ) by the infiltrating CD4+ T cells modulates vasculature permeability, which allows access of protective antibodies to infected neurons to limit viral spreading. Curiously, the route of immunization also influences whether protective responses can be elicited. Whether this last finding is due to eliciting a particular antibody isotype or proper homing properties of the CD4+ T cells remains unknown.

Nature (18 May 2016) doi:10.1038/nature17979