Cellular and soluble factor requirements for induction of cytotoxic T lymphocytes against herpes simplex virus type 1

The cell types required for the induction of cytotoxic T lymphocyte responses to herpes simplex virus were characterized. The cells were analyzed with respect to their role in induction, activation requirements, and their cell surface antigen profiles. At least three cell types are apparently involved in the generation of anti-HSV CTL: a CTL precursor, a helper T lymphocyte, and an adherent accessory cell. The accessory cell, which could be effectively separated from whole splenocyte suspensions by virtue of its differential adherence to glass, plastic, nylon wool, or Sephadex G-10, needed to express Ia antigens in its membrane. In addition, the adherent accessory cell must be capable of secreting the macrophage-derived soluble factor, interleukin-1. These studies also suggested that the Ia-positive accessory cell has as its role the activation of helper T lymphocytes (HTL), which are also a required cell type for anti-herpes CTL induction.

Helper T lymphocytes exposed to infectious HSV-1 presented on the surface of accessory cells in addition to interleukin-1, respond with the production of nonspecific factors that drive antigen-stimulated CTL precursors on to maturity. Heat or UV light-inactivated preparations of HSV-1 were unable to stimulate helper cell activity in vitro or in vivo. The results suggest that inactivated HSV-1 fails to stimulate due to a lack of recognition by HTL, rather than by the induction of active suppression.

The third cell type required for CTL induction, the CTL precursor, could be stimulated effectively by inactivated forms of HSV-1, at least in vitro. These results thus indicate a differential antigen activation requirement for CTL and HTL precursors.