Innate-like T cells straddle innate and adaptive immunity by altering antigen-receptor responsiveness

Melanie Wencker; Gleb Turchinovich; Rafael Di Marco Barros; Livija Deban; Anett Jandke; Andrew Cope; Adrian C Hayday

doi:10.1038/ni.2773

Innate-like T cells straddle innate and adaptive immunity by altering antigen-receptor responsiveness

Nat Immunol. 2014 Jan;15(1):80-7. doi: 10.1038/ni.2773. Epub 2013 Nov 17.

Authors

Melanie Wencker¹, Gleb Turchinovich², Rafael Di Marco Barros³, Livija Deban⁴, Anett Jandke⁴, Andrew Cope⁵, Adrian C Hayday⁶

Affiliations

¹ 1] London Research Institute, Cancer Research UK, London, UK. [2] Peter Gorer Department of Immunobiology, King's College London, London, UK. [3] These authors contributed equally to this work.
² 1] London Research Institute, Cancer Research UK, London, UK. [2] Peter Gorer Department of Immunobiology, King's College London, London, UK. [3] Present address: Department of Biomedicine, University of Basel, Basel, Switzerland. [4] These authors contributed equally to this work.
³ 1] London Research Institute, Cancer Research UK, London, UK. [2] University College London, London, UK.
⁴ London Research Institute, Cancer Research UK, London, UK.
⁵ Centre for the Molecular and Cell Biology of Inflammation, King's College London, London, UK.
⁶ 1] London Research Institute, Cancer Research UK, London, UK. [2] Peter Gorer Department of Immunobiology, King's College London, London, UK.

PMID: 24241693
PMCID: PMC6485477
DOI: 10.1038/ni.2773

Abstract

The subclassification of immunology into innate and adaptive immunity is challenged by innate-like T lymphocytes that use innate receptors to respond rapidly to stress despite expressing T cell antigen receptors (TCRs), a hallmark of adaptive immunity. In studies that explain how such cells can straddle innate and adaptive immunity, we found that signaling via antigen receptors, whose conventional role is to facilitate clonal T cell activation, was critical for the development of innate-like T cells but then was rapidly attenuated, which accommodated the cells' innate responsiveness. These findings permitted the identification of a previously unknown innate-like T cell subset and indicate that T cell hyporesponsiveness, a state traditionally linked to tolerance, may be fundamental to T cells entering the innate compartment and thereby providing lymphoid stress surveillance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity / immunology*
Animals
Animals, Newborn
Cells, Cultured
Flow Cytometry
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Immunity, Innate / immunology*
Interleukin-17 / immunology
Interleukin-17 / metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
Nuclear Receptor Subfamily 4, Group A, Member 1 / immunology
Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism
Receptors, Antigen, T-Cell / immunology*
Receptors, Antigen, T-Cell / metabolism
Receptors, Antigen, T-Cell, gamma-delta / immunology
Receptors, Antigen, T-Cell, gamma-delta / metabolism
Signal Transduction / immunology
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism
ZAP-70 Protein-Tyrosine Kinase / immunology
ZAP-70 Protein-Tyrosine Kinase / metabolism

Substances

Interleukin-17
Nuclear Receptor Subfamily 4, Group A, Member 1
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, gamma-delta
Green Fluorescent Proteins
ZAP-70 Protein-Tyrosine Kinase
Zap70 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding