Cutting edge: Induction of follicular homing precedes effector Th cell development

Transition from naive to Ag-experienced effector/memory CD4(+) T cells is initiated during contact with APC in secondary lymphoid tissue. Here, we demonstrate that the CXCR5 is a marker for recently activated memory CD4(+) T cells. CXCR5 is rapidly induced during contact with Ag-presenting dendritic cells, well before T cell expansion and effector cell development, and is irreversibly lost on terminally differentiated effector cells. Furthermore, immunization of human volunteers with a recall Ag results in rapid accumulation of Ag-responsive, CXCR5-expressing CD4(+) T cells in peripheral blood. Early acquisition of a new migration program enables T zone CD4(+) T cells to develop into follicular B helper T cells or, alternatively, into circulating memory CD4(+) T cells. Together, CXCR5 unequivocally defines pre-effector memory CD4(+) T cells generated during ongoing immune responses.