CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help

CD4(+) T helper cells are well known for their role in providing critical signals during priming of cytotoxic CD8(+) T lymphocyte (CTL) responses in vivo. T-cell help is required for the generation of primary CTL responses as well as in promoting protective CD8(+) memory T-cell development. However, the role of CD4 help in the control of CTL responses at the effector stage is unknown. Here we show that fully helped effector CTLs are themselves not self-sufficient for entry into the infected tissue, but rely on the CD4(+) T cells to provide the necessary cue. CD4(+) T helper cells control the migration of CTL indirectly through the secretion of IFN-gamma and induction of local chemokine secretion in the infected tissue. Our results reveal a previously unappreciated role of CD4 help in mobilizing effector CTL to the peripheral sites of infection where they help to eliminate infected cells.