Quantitative studies on CD4+ and CD8+ cytotoxic T lymphocyte responses against herpes simplex virus type 1 in normal and β2-m deficient mice

Against herpes simplex virus type 1 (HSV-1) infected target cells, effector T cells of both CD4− CD8+ and CD4+ CD8− phenotypes occur in both man and mice. In man, the CD4+ CD8− phenotype may dominate the response, but the situation in the mouse is unclear. In this report, several approaches are used to document the existence of HSV-1-specific cytotoxic T lymphocytes (CTL) of both phenotypes and to quantitate the frequency of their CTL precursors (CTL-p) in acutely HSV-1 infected animals. Evidence that CD4+ CD8− CTL occur was confirmed with β2-m− mice lacking CD8+ T cells and which generated CTL capable only of lysing MHC class II infected target cells. Comparisons of frequencies of CD4+ CD8− and CD4− CD8+ CTL-p showed the former to be 2–3-fold more frequent. The β2-m− mice generated only CD4+ CD8− CTL-p and their frequencies approximately equally the CD4+ CD8− CTL-p frequency in intact infected mice. Our results are discussed in terms of the value of the mouse model to study HSV-1 immunobiology.