title: Early-life compartmentalization of human T cell differentiation and regulatory function in mucosal and lymphoid tissues.
abstract: It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity and immunoregulation. In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells, in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T(EM)) found only in the lungs and small intestine. Additionally, regulatory T (T(reg)) cells comprise a high proportion (30-40%) of CD4(+) T cells in pediatric tissues but are present at much lower frequencies (1-10%) in adult tissues. Pediatric tissue T(reg) cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T(reg):T(EM) cell ratios, which suggests control in situ of immune responses in early life.
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Joseph J C
authors.initials: JJ
authors.lastname: Thome
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Bickham
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohmura
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Matsuoka
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.|Department of Medicine, Columbia University Medical Center, New York, New York, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Gordon
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Tomer
authors.initials: T
authors.lastname: Granot
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Griesemer
authors.affiliation: LiveOnNY, New York, New York, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Lerner
authors.affiliation: Department of Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.|Department of Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Donna L
authors.identifier: http://orcid.org/0000-0001-8236-9183
authors.initials: DL
authors.lastname: Farber
mesh_terms: D000293:Adolescent; D000328:Adult; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000276:immunology; D007422:Intestines / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines