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.