From crucial to negligible: Functional CD8+ T-cell responses and their dependence on CD4+ T-cell help

CD8+ T cells play an important role in controlling pathogenic infections and are therefore key players in the immune response. It has been shown that among other factors CD4+ T cells can shape the magnitude as well as the quality of primary and/or secondary CD8+ T-cell responses. However, due to the complexity and the differences among diverse immunization or infection models, the overall requirement, the time points, as well as the specific mechanism(s) of CD4+ T-cell help may differ substantially. Here, we summarize current knowledge about the differential requirement of CD4+ T-cell help in promoting primary CD8+ T-cell responses as well as establishing functional memory CD8+ T cells in various experimental settings.