- Herpes simplex virus type 2 (HSV-2) is a human venereal pathogen that causes lethal neurological illness after intravaginal inoculation into BALB/cJ mice. Intravaginal vaccination of mice with an attenuated strain of HSV-2 rapidly induces immunity to a lethal intravaginal challenge with wild-type HSV-2. This resistance is transferrable to syngeneic mice with genital lymph node (GLN) cells but not with cells from other lymphoid sources. Here we demonstrate that minimal numbers of HSV-2-stimulated GLN T lymphocytes are required for resistance to genital infection by HSV-2 and that such cells migrate preferentially into HSV-2-infected genital tissue. Furthermore, the results suggest that HSV-2-specific cytotoxic T lymphocytes from the GLN may be one effector cell population participating locally in genital immunity to the virus. These findings indicate that mucosal immunity to genital HSV-2 infection requires the antigen stimulation of migratory T cells in the GLN.