Chemokine Guidance of Central Memory T Cells Is Critical for Antiviral Recall Responses in Lymph Nodes

A defining feature of vertebrate immunity is the acquisition of immunological memory, which confers enhanced protection against pathogens by mechanisms that are incompletely understood. Here, we compared responses by virus-specific naive T cells (T-N) and central memory T cells (T-CM) to viral antigen challenge in lymph nodes (LNs). In steady-state LNs, both T cell subsets localized in the deep T cell area and interacted similarly with antigen-presenting dendritic cells. However, upon entry of lymph-borne virus, only T-CM relocalized rapidly and efficiently toward the outermost LN regions in the medullary, interfollicular, and subcapsular areas where viral infection was initially confined. This rapid peripheralization was coordinated by a cascade of cytokines and chemokines, particularly ligands for T-CM-expressed CXCR3. Consequently, in vivo recall responses to viral infection by CXCR3-deficient T-CM were markedly compromised, indicating that early antigen detection afforded by intranodal chemokine guidance of T-CM is essential for efficient antiviral memory.