Infiltration of T-lymphocytes in the brain after anterior chamber inoculation of a neurovirulent and neuroinvasive strain of HSV-1.

Following anterior chamber (AC) inoculation of BALB/c mice with the KOS strain of herpes simplex virus type 1 (HSV-1), or with H129, a neuroinvasive and neurovirulent strain of HSV-1, both strains of virus spread from the injected eye through the brain to cause retinitis. However, KOS-infected mice develop retinitis in the uninoculated eye only, whereas H129-infected mice develop bilateral retinitis. Previous studies have shown that infiltrating T-cells in the suprachiasmatic nuclei (SCN) of the hypothalamus of KOS-infected mice concomitant with or before virus protect KOS-infected mice from ipsilateral retinitis. To determine the timing of T cell infiltration and cytokine production in the brain of H129-infected mice, adjacent, frozen sections of the brain were immunostained for virus, T-cells, IL-2, TNF-alpha or IFN-gamma. T-cells infiltrated the brains of H129-infected mice and cytokines were produced in infected tissues. However, virus spread to the optic nerve and retina of both the inoculated and uninoculated eye before T-cells and cytokines were detected in the SCN of H129-infected mice. These results suggest that infiltrating T-cells in the SCN of H129-infected mice may arrive too late to prevent the spread of virus into the optic nerves and retinas and thus prevent development of bilateral retinitis in infected mice.