Protection from herpes simplex virus-induced neuropathology in mice showing delayed hypersensitivity tolerance.

Herpes simplex virus (HSV)-susceptible mice inoculated under conditions favouring the preferential activation of T suppressor (Ts) cells acting on the delayed-type hypersensitivity (DTH) response to the virus were protected from lethal herpes encephalitis and from central nervous system (CNS) demyelination (as reflected by ear paralysis), compared to controls given normal priming. Thus, suppressed DTH was not incompatible with recovery from acute infection and may indeed have been beneficial. Protection could be transferred by T cells from donors given a 'DTH-tolerogenic' priming regime. It was unlikely that protection resulted from enhancement of other mechanisms such as cytotoxic T cell activation, antibody or interferon production, since no reduction of virus spread was observed in protected mice. In addition, several aspects of Ts cell activation by intravenous inoculation of avirulent HSV type 1 have been characterized. Suppression was virus dose-dependent and could be transferred to the efferent limb of a DTH response. Activation of Ts cells for DTH coincided with an enhanced antibody response. It is suggested that protection in this model may be mediated by Ts cells which act to limit DTH-mediated immunopathology in the CNS.