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

• Published in: Cell Vol. 150; no. 6; pp. 1249 - 1263
• Main Authors: Sung, Jung Hwan, Zhang, Han, Moseman, E. Ashley, Alvarez, David, Iannacone, Matteo, Henrickson, Sarah E., de la Torre, Juan C., Groom, Joanna R., Luster, Andrew D., von Andrian, Ulrich H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.09.2012
• Subjects: Animals; antigen detection; antigens; CD8-Positive T-Lymphocytes - immunology; Chemokine CXCL9 - immunology; chemokines; CXCR3 receptor; dendritic cells; Dendritic Cells - immunology; Immunologic Memory; Interferon-gamma - immunology; ligands; lymph nodes; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocytic choriomeningitis virus; Mice; Mice, Inbred C57BL; Monocytes - immunology; pathogens; Receptors, Antigen, T-Cell - metabolism; Receptors, CXCR3 - immunology; Stromal Cells - immunology; T-Lymphocyte Subsets - immunology; T-lymphocytes; vertebrates; Vesicular stomatitis Indiana virus; viral antigens; viruses
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2012.08.015

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 (TN) and central memory T cells (TCM) 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 TCM 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 TCM-expressed CXCR3. Consequently, in vivo recall responses to viral infection by CXCR3-deficient TCM were markedly compromised, indicating that early antigen detection afforded by intranodal chemokine guidance of TCM is essential for efficient antiviral memory. [Display omitted] ► CXCR3+ TCM and CXCR3− TN differentially respond to viral infections in lymph nodes ► CXCL10 and CXCL9 are induced by IFN-I and IFNγ from macrophages and TCM, respectively ► CXCL9 and CXCL10 guide CXCR3+ TCM toward viral antigens in the lymph node periphery ► CXCR3 guidance is essential for efficient antiviral recall responses by TCM Chemokines ensure that memory T cells in the lymph node gain rapid access to viral antigens by guiding them to sites of viral entry. This facilitated exposure is important for the development of immunological memory.