Mononucleosis and Antigen-Driven T Cell Responses Have Different Requirements for Interleukin-2 Signaling in Murine

Interleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8 T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8 T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8 T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required for CD8 T cell mononucleosis. Members of the gammaherpesvirus family are associated with significant diseases, such as nasopharyngeal carcinoma, lymphoid malignancies, and infectious mononucleosis (16). Murine gammaherpesvirus 68 (MHV-68) is a 2-herpesvirus related to the human pathogens Epstein-Barr virus (EBV) and Kaposi’s sarcoma virus (19, 21). Intranasal (i.n.) infection of mice with MHV-68 results in acute infection of the lung epi-thelium, which is eventually controlled; however, the virus als