Abstract

There is an urgent need to develop novel therapies for controlling recurrent virus infections in immune suppressed patients. Disease associated with persistent gamma-herpesvirus infection (EBV, HHV-8) is a significant problem in AIDS patients and transplant recipients, and clinical management of these conditions is difficult. Disease occurs because of a failure in immune surveillance to control the persistent infection, which arises in AIDS patients principally because of an erosion of the CD4(+) T cell compartment. Immune surveillance failure followed by gamma-herpesvirus recrudescence can be modeled using murine gamma-herpesvirus in CD4 T cell-depleted mice. We show that enhancement of IL-2 signaling using IL-2/anti-IL-2 immune complexes substantially improves immune surveillance in the context of suppressed immunity and enhances control of the infection. This effect was not due solely to increased numbers of virus-specific CD8 T cells but rather to enhanced cytotoxicity mediated by the perforin-granzyme pathway.