title: Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8(+) T cell differentiation by a CD24-dependent mechanism.
abstract: The contribution of different DC subsets to effector and memory CD8(+) T cell generation during infection and the mechanism by which DCs controls these fate decisions is unclear. Here we demonstrated that the CD103(+) and CD11b(hi) migratory respiratory DC (RDC) subsets after influenza virus infection activated naive virus-specific CD8(+) T cells differentially. CD103(+) RDCs supported the generation of CD8(+) T effector (Teff) cells, which migrate from lymph nodes to the infected lungs. In contrast, migrant CD11b(hi) RDCs activated CD8(+) T cells characteristic of central memory CD8(+) T (CD8(+) Tcm) cells including retention within the draining lymph nodes. CD103(+) RDCs expressed CD24 at an elevated level, contributing to the propensity of this DC subpopulation to support CD8(+) Teff cell differentiation. Mechanistically, CD24 was shown to regulate CD8(+) T cell activation through HMGB1-mediated engagement of T cell RAGE. Thus, there is distribution of labor among DC subsets in regulating CD8(+) T cell differentiation.
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Taeg S
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Gorski
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA; Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA; Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: tjb2r@virginia.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007156:Immunologic Memory; D016130:Immunophenotyping; D039001:Integrin alpha Chains / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011485:Protein Binding; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D057074:Virus Release / Q000276:immunology
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D051927:CD24 Antigen; D039001:Integrin alpha Chains; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C091367:alpha E integrins