Expanding roles for CD4+ T cells in immunity to viruses

Immunity to viruses is typically associated with the development of cytotoxic CD8+ T cells. However, CD4+ T cells are also important for protection during viral infection. Here, the authors describe the various ways in which different CD4+T cell subsets can contribute to the antiviral immune response. Viral pathogens often induce strong effector CD4+ T cell responses that are best known for their ability to help B cell and CD8+ T cell responses. However, recent studies have uncovered additional roles for CD4+ T cells, some of which are independent of other lymphocytes, and have described previously unappreciated functions for memory CD4+ T cells in immunity to viruses. Here, we review the full range of antiviral functions of CD4+ T cells, discussing the activities of these cells in helping other lymphocytes and in inducing innate immune responses, as well as their direct antiviral roles. We suggest that all of these functions of CD4+ T cells are integrated to provide highly effective immune protection against viral pathogens.