Functional cytotoxic T cells are associated with focal lesions in the brains of SJL mice with experimental herpes simplex encephalitis

Abstract

Using a recently developed murine model of herpes simplex encephalitis in SJL mice, we isolated and characterized brain-infiltrating mononuclear cells to identify immune effectors that might contribute to pathology in this disease. Brain infiltrating mononuclear cells obtained from temporal area lesions were found to be predominantly T cells, with CD4+ and CD8+ T cell types present in equal numbers. The herpes simplex virus type 1 (HSV-1)-specific CTL that were present within the temporal area of HSV-1 infected SJL mice were fully activated (i.e., they did not require in vitro culture to acquire cytotoxic function). These cells were Thy-1.2+, CD8+ and exhibited the classical features of CTL activity: Ag specificity and MHC restriction. To our knowledge this is the first definitive demonstration of HSV-1-specific CTL activity directly ex vivo in mice. Freshly isolated spleen or lymph node cells from the same mice failed to exhibit CTL activity. The lytic capacity of infiltrating cells appeared to be mediated exclusively by CTL because treatment with Abs to Thy-1.2, or CD8, and C completely removed cytotoxic activity. NK cell activity was not detected in spleen, lymph node, or brain-infiltrating mononuclear cells from SJL mice with HSV encephalitis. Significantly, T cells were the prominent cell type in the temporal area of HSV-1-infected SJL mice just before the development of focal lesions, with CD8+ cells being present in equal or greater numbers than CD4+ cells (a CD4:CD8 ratio of 1 < or = 1). Thus, the accumulation of functional CD8+ CTL in the temporal area of the brain correlated with the occurrence of focal entorhinal lesions.