1. Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
2. Pulmonary Division, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

Correspondence to: Akiko Iwasaki¹ Correspondence and requests for materials should be addressed to A.I. (Email: akiko.iwasaki@yale.edu).

Abstract

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 development¹. 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- 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.