Innate-like T cells straddle innate and adaptive immunity by altering antigen-receptor responsiveness.
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.
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.
Melanie
M
Wencker
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.
Gleb
G
Turchinovich
1] London Research Institute, Cancer Research UK, London, UK. [2] University College London, London, UK.
Rafael
R
Di Marco Barros
London Research Institute, Cancer Research UK, London, UK.
Livija
L
Deban
London Research Institute, Cancer Research UK, London, UK.
Anett
A
Jandke
Centre for the Molecular and Cell Biology of Inflammation, King's College London, London, UK.
Andrew
A
Cope
1] London Research Institute, Cancer Research UK, London, UK. [2] Peter Gorer Department of Immunobiology, King's College London, London, UK.
Adrian C
AC
Hayday
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology / Q000378:metabolism
D020381:Interleukin-17; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D049452:Green Fluorescent Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse