title: Differential Intrasplenic Migration of Dendritic Cell Subsets Tailors Adaptive Immunity.
abstract: Evidence suggests that distinct splenic dendritic cell (DC) subsets activate either CD4+ or CD8+ T cells in vivo. This bias has been partially ascribed to differential antigen presentation; however, all DC subsets can activate both T cell lineages in vitro. Therefore, we tested whether the organization of DC and T cell subsets in the spleen dictated this preference. We discovered that CD4+ and CD8+ T cells segregated within splenic T cell zones prior to immunization. After intravenous immunization, the two major conventional DC populations, distinguished by 33D1 and XCR1 staining, migrated into separate regions of the T cell zone: 33D1+ DCs migrated into the CD4+ T cell area, whereas XCR1+ DCs migrated into the CD8+ T cell area. Thus, the post-immunization location of each DC subset correlated with the T cell lineage it preferentially primes. Preventing this co-localization selectively impaired either CD4+ or CD8+ T cell immunity to blood-borne antigens.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Roche Pharma Research and Early Development, Roche Innovation Center Zurich, 8952 Schlieren, Switzerland.
authors.forename: Samuele
authors.initials: S
authors.lastname: Calabro
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Antonia
authors.initials: A
authors.lastname: Gallman
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil.
authors.forename: Manuela Sales L
authors.initials: MS
authors.lastname: Nascimento
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Zizi
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Yuexiu, Guangzhou, Guangdong 510080, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Biyan
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Uthaman
authors.initials: U
authors.lastname: Gowthaman
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Respiratory, Inflammation and Autoimmunity, Innovative Medicines and Early Development, AstraZeneca, 431 50 Mölndal, Sweden.
authors.forename: Jayendra Kumar
authors.initials: JK
authors.lastname: Krishnaswamy
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Haberman
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT 06032, USA. Electronic address: adam.williams@jax.org.
authors.forename: Adam
authors.initials: A
authors.lastname: Williams
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: stephanie.eisenbarth@yale.edu.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Eisenbarth
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D003713:Dendritic Cells / Q000145:classification* / Q000166:cytology / Q000276:immunology; D017707:Erythrocyte Transfusion; D015870:Gene Expression; D007114:Immunization; D016130:Immunophenotyping; D007518:Isoantibodies / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology*
chemical_list: D000941:Antigens; D015415:Biomarkers; D007518:Isoantibodies; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; C551408:XC chemokine receptor 1, mouse; D010047:Ovalbumin
keywords: CCR7; T cell; dendritic cell; red blood cell alloimmunization; spleen