Distinct populations of CD4+ T cells regulate the virus-specific immune response during acute Friend Retrovirus infection. CD4+ helper T cells and follicular helper T cells augment virus-specific cytotoxic T cell and antibody responses. In addition, a subpopulation of effector CD4+ T cells directly inhibits virus replication. However, at the same time natural regulatory T cells expand and start to suppress effector T cell responses, which interferes with control of virus replication. (Arrows indicate enhancement of responses, whereas blocked lines indicate inhibition).