Single cell behavior in T cell differentiation

•Upon antigen encounter, proliferating T cells diversify in function and phenotype.•Lineage tracing demonstrates that the output of individual T cells is highly variable.•Reproducibility of T cell responses is due to the averaging of disparate single cell behaviors.•Variability in T cell output may...

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Vydáno v:	Trends in immunology Ročník 35; číslo 4; s. 170 - 177
Hlavní autoři:	Rohr, Jan C., Gerlach, Carmen, Kok, Lianne, Schumacher, Ton N.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Ltd 01.04.2014 Elsevier Limited
Témata:	Allergy and Immunology Animals Antigens Apoptosis asymmetric cell division Asymmetry Behavior Cell Differentiation - immunology Cell division cell-extrinsic signals cellular heterogeneity Daughters Epigenetics Humans Immunology Infections Lymphocyte Activation - immunology Lymphocytes Population population asymmetry single-cell tracking Stem cells Studies T cell differentiation T-Lymphocytes - cytology T-Lymphocytes - immunology asymmetric cell division cellular heterogeneity cell-extrinsic signals single-cell tracking population asymmetry T cell differentiation
ISSN:	1471-4906, 1471-4981, 1471-4981
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Abstract	•Upon antigen encounter, proliferating T cells diversify in function and phenotype.•Lineage tracing demonstrates that the output of individual T cells is highly variable.•Reproducibility of T cell responses is due to the averaging of disparate single cell behaviors.•Variability in T cell output may be driven by cell-intrinsic or cell-extrinsic mechanisms. Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field.
AbstractList	Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field. Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field.Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field. •Upon antigen encounter, proliferating T cells diversify in function and phenotype.•Lineage tracing demonstrates that the output of individual T cells is highly variable.•Reproducibility of T cell responses is due to the averaging of disparate single cell behaviors.•Variability in T cell output may be driven by cell-intrinsic or cell-extrinsic mechanisms. Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various subsets. A long-standing question in the field has been how this cellular diversification is achieved. Conceptually, diverse cellular output may either arise from every single cell or only from populations of naïve cells. Furthermore, such diversity may either be driven by cell-intrinsic heterogeneity or by external, niche-derived signals. In this review, we discuss how recently developed technologies have allowed the analysis of the mechanisms underlying T cell diversification at the single cell level. In addition, we outline the implications of this work on our understanding of the formation of immunological memory, and describe a number of unresolved key questions in this field. Highlights • Upon antigen encounter, proliferating T cells diversify in function and phenotype. • Lineage tracing demonstrates that the output of individual T cells is highly variable. • Reproducibility of T cell responses is due to the averaging of disparate single cell behaviors. • Variability in T cell output may be driven by cell-intrinsic or cell-extrinsic mechanisms.
Author	Gerlach, Carmen Rohr, Jan C. Schumacher, Ton N. Kok, Lianne
Author_xml	– sequence: 1 givenname: Jan C. surname: Rohr fullname: Rohr, Jan C. organization: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 2 givenname: Carmen surname: Gerlach fullname: Gerlach, Carmen organization: Department of Microbiology & Immunobiology, Harvard Medical School, Boston, MA, USA – sequence: 3 givenname: Lianne surname: Kok fullname: Kok, Lianne organization: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands – sequence: 4 givenname: Ton N. surname: Schumacher fullname: Schumacher, Ton N. email: t.schumacher@nki.nl organization: Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
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Immunol. doi: 10.4049/jimmunol.167.9.4838
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Snippet	•Upon antigen encounter, proliferating T cells diversify in function and phenotype.•Lineage tracing demonstrates that the output of individual T cells is... Highlights • Upon antigen encounter, proliferating T cells diversify in function and phenotype. • Lineage tracing demonstrates that the output of individual T... Upon primary infection, naïve T cells that recognize their cognate antigen become activated, proliferate, and simultaneously differentiate into various...
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SubjectTerms	Allergy and Immunology Animals Antigens Apoptosis asymmetric cell division Asymmetry Behavior Cell Differentiation - immunology Cell division cell-extrinsic signals cellular heterogeneity Daughters Epigenetics Humans Immunology Infections Lymphocyte Activation - immunology Lymphocytes Population population asymmetry single-cell tracking Stem cells Studies T cell differentiation T-Lymphocytes - cytology T-Lymphocytes - immunology
Title	Single cell behavior in T cell differentiation
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