CD4 and influenza: However, the protective role of this heterosubtypic immunity is debatable with conflicting evidence for pre-existing CD4+, but not CD8+, T-cells associated with lower virus shedding and less severe illness in mouse models of influenza [43,44] whilst others have reported viral clearance mediated by antigen-specific CD8+ effector T-cells, with a role for CD4+ T-cells in maintaining CD8+ T and B-cell memory responses [45].