Immunohistochemical Examination of Intracerebral T Cell Recruitment and Adhesion Molecule Induction in Herpes Simplex Virus-Infected Mice

Abstract

Herpes simplex virus type 1 (HSV-1) infection in the nervous system is tightly controlled by the T-cell-mediated response. This report describes the temporal relationships among HSV-1 infection, intracerebral adhesion molecule induction, and T cell migration in intravitreally inoculated mice. HSV-1 immunoreactivity, initially detected at 3 days, increased in area and intensity in the superior colliculus, oculomotor nucleus, and geniculate through 5 days. By 6 days, HSV-1 was nearly undetectable in the same regions and the mice survive the infection. At the peak of HSV-1 immunoreactivity, ICAM-1 and VCAM-1 were strongly expressed in all infected brain regions. Additionally, in these region a few CD4+and CD8+T cells were detected. The heaviest T cell migration and adhesion molecule expression occurred at 6 days, coinciding with the decrease in HSV-1 immunoreactivity. However, in SCID and athymic mice, HSV-1 was not cleared from the brain and the mice died. Together, these data suggest that HSV-1 infection of the brain is followed by adhesion molecule induction in and T cell extravasation into the infected brain regions. Most importantly, an efficient T cell response was required to eradicate infectious HSV-1 from the brain.