title: Chemokine guidance of central memory T cells is critical for antiviral recall responses in lymph nodes.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Sung
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: E Ashley
authors.initials: EA
authors.lastname: Moseman
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.forename: Matteo
authors.initials: M
authors.lastname: Iannacone
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Henrickson
authors.forename: Juan C
authors.initials: JC
authors.lastname: de la Torre
authors.forename: Joanna R
authors.initials: JR
authors.lastname: Groom
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054370:Chemokine CXCL9 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus
chemical_list: D054370:Chemokine CXCL9; C515188:Cxcr3 protein, mouse; D011948:Receptors, Antigen, T-Cell; D054367:Receptors, CXCR3; D007371:Interferon-gamma