title: Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.
abstract: Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143-1234, USA.
authors.forename: Jeff E
authors.initials: JE
authors.lastname: Mold
authors.forename: Shivkumar
authors.initials: S
authors.lastname: Venkatasubrahmanyam
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Burt
authors.forename: Jakob
authors.initials: J
authors.lastname: Michaëlsson
authors.forename: Jose M
authors.initials: JM
authors.lastname: Rivera
authors.forename: Sofiya A
authors.initials: SA
authors.lastname: Galkina
authors.forename: Kenneth
authors.initials: K
authors.lastname: Weinberg
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Stoddart
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology; D000375:Aging / Q000276:immunology; D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019070:Cell Lineage; D019610:Cytoprotection; D005333:Fetus / Q000166:cytology / Q000276:immunology*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008099:Liver / Q000166:cytology / Q000196:embryology; D008213:Lymphocyte Activation; D038041:Lymphopoiesis; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D055815:Young Adult