A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

Sarah C. Edwards; Caroline E. Sutton; Kristin Ladell; Emma J. Grant; James E. McLaren; Fiona Roche; Pradyot Dash; Nopporn Apiwattanakul; Walid Awad; Kelly L. Miners; Stephen J. Lalor; Julie C. Ribot; Song Baik; Barry Moran; Aoife McGinley; Valerie Pivorunas; Lori Dowding; Michael Macoritto; Jesus Paez-Cortez; Anthony Slavin; Graham Anderson; Bruno Silva-Santos; Karsten Hokamp; David A. Price; Paul G. Thomas; Rachel M. McLoughlin; Kingston H.G. Mills

doi:10.1084/jem.20190834

A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

Sarah C. Edwards, Caroline E. Sutton, Kristin Ladell, Emma J. Grant, James E. McLaren, Fiona Roche, Pradyot Dash, Nopporn Apiwattanakul, Walid Awad, Kelly L. Miners, Stephen J. Lalor, Julie C. Ribot, Song Baik, Barry Moran, Aoife McGinley, Valerie Pivorunas, Lori Dowding, Michael Macoritto, Jesus Paez-Cortez, Anthony SlavinGraham Anderson, Bruno Silva-Santos, Karsten Hokamp, David A. Price, Paul G. Thomas, Rachel M. McLoughlin, Kingston H.G. Mills^*

^*Corresponding author for this work

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4⁺ or CD8⁺ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.

Original language	English
Article number	e20190834
Journal	Journal of Experimental Medicine
Volume	217
Issue number	5
DOIs	https://doi.org/10.1084/jem.20190834
Publication status	Published - 4 May 2020

Bibliographical note

Funding Information:
This work was supported by grants from Science Foundation Ireland (15/IA/3041 to R.M. McLoughlin and 11/PI/1036, 12/RI/ 2340(7), 15/SPP/3212, and 16/IA/4468 to K.H.G. Mills), AbbVie (to K.H.G. Mills), Irish Higher Education Authority Program for Research in Third-Level Institutions (to S.C. Edwards and K.H.G. Mills), National Health and Medical Research Council (a CJ Martin ECR Fellowship to E.J. Grant), European Research Council (CoG_646701 to B. Silva-Santos), Medical Research Council (G1000213 to G. Anderson), Wellcome Trust (100326Z/12/Z to D.A. Price), National Institutes of Health (RO1AI107625 to P.G. Thomas), and American Lebanese Syrian Associated Charities (to P.G. Thomas).

Publisher Copyright:
© 2020 Edwards et al.

ASJC Scopus subject areas

General Medicine

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10.1084/jem.20190834

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Edwards, S. C., Sutton, C. E., Ladell, K., Grant, E. J., McLaren, J. E., Roche, F., Dash, P., Apiwattanakul, N., Awad, W., Miners, K. L., Lalor, S. J., Ribot, J. C., Baik, S., Moran, B., McGinley, A., Pivorunas, V., Dowding, L., Macoritto, M., Paez-Cortez, J., ... Mills, K. H. G. (2020). A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans. Journal of Experimental Medicine, 217(5), Article e20190834. https://doi.org/10.1084/jem.20190834

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title = "A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans",

abstract = "T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.",

author = "Edwards, {Sarah C.} and Sutton, {Caroline E.} and Kristin Ladell and Grant, {Emma J.} and McLaren, {James E.} and Fiona Roche and Pradyot Dash and Nopporn Apiwattanakul and Walid Awad and Miners, {Kelly L.} and Lalor, {Stephen J.} and Ribot, {Julie C.} and Song Baik and Barry Moran and Aoife McGinley and Valerie Pivorunas and Lori Dowding and Michael Macoritto and Jesus Paez-Cortez and Anthony Slavin and Graham Anderson and Bruno Silva-Santos and Karsten Hokamp and Price, {David A.} and Thomas, {Paul G.} and McLoughlin, {Rachel M.} and Mills, {Kingston H.G.}",

note = "Funding Information: This work was supported by grants from Science Foundation Ireland (15/IA/3041 to R.M. McLoughlin and 11/PI/1036, 12/RI/ 2340(7), 15/SPP/3212, and 16/IA/4468 to K.H.G. Mills), AbbVie (to K.H.G. Mills), Irish Higher Education Authority Program for Research in Third-Level Institutions (to S.C. Edwards and K.H.G. Mills), National Health and Medical Research Council (a CJ Martin ECR Fellowship to E.J. Grant), European Research Council (CoG_646701 to B. Silva-Santos), Medical Research Council (G1000213 to G. Anderson), Wellcome Trust (100326Z/12/Z to D.A. Price), National Institutes of Health (RO1AI107625 to P.G. Thomas), and American Lebanese Syrian Associated Charities (to P.G. Thomas). Publisher Copyright: {\textcopyright} 2020 Edwards et al.",

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Edwards, SC, Sutton, CE, Ladell, K, Grant, EJ, McLaren, JE, Roche, F, Dash, P, Apiwattanakul, N, Awad, W, Miners, KL, Lalor, SJ, Ribot, JC, Baik, S, Moran, B, McGinley, A, Pivorunas, V, Dowding, L, Macoritto, M, Paez-Cortez, J, Slavin, A, Anderson, G, Silva-Santos, B, Hokamp, K, Price, DA, Thomas, PG, McLoughlin, RM & Mills, KHG 2020, 'A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans', Journal of Experimental Medicine, vol. 217, no. 5, e20190834. https://doi.org/10.1084/jem.20190834

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T1 - A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

AU - Edwards, Sarah C.

AU - Sutton, Caroline E.

AU - Ladell, Kristin

AU - Grant, Emma J.

AU - McLaren, James E.

AU - Roche, Fiona

AU - Dash, Pradyot

AU - Apiwattanakul, Nopporn

AU - Awad, Walid

AU - Miners, Kelly L.

AU - Lalor, Stephen J.

AU - Ribot, Julie C.

AU - Baik, Song

AU - Moran, Barry

AU - McGinley, Aoife

AU - Pivorunas, Valerie

AU - Dowding, Lori

AU - Macoritto, Michael

AU - Paez-Cortez, Jesus

AU - Slavin, Anthony

AU - Anderson, Graham

AU - Silva-Santos, Bruno

AU - Hokamp, Karsten

AU - Price, David A.

AU - Thomas, Paul G.

AU - McLoughlin, Rachel M.

AU - Mills, Kingston H.G.

N1 - Funding Information: This work was supported by grants from Science Foundation Ireland (15/IA/3041 to R.M. McLoughlin and 11/PI/1036, 12/RI/ 2340(7), 15/SPP/3212, and 16/IA/4468 to K.H.G. Mills), AbbVie (to K.H.G. Mills), Irish Higher Education Authority Program for Research in Third-Level Institutions (to S.C. Edwards and K.H.G. Mills), National Health and Medical Research Council (a CJ Martin ECR Fellowship to E.J. Grant), European Research Council (CoG_646701 to B. Silva-Santos), Medical Research Council (G1000213 to G. Anderson), Wellcome Trust (100326Z/12/Z to D.A. Price), National Institutes of Health (RO1AI107625 to P.G. Thomas), and American Lebanese Syrian Associated Charities (to P.G. Thomas). Publisher Copyright: © 2020 Edwards et al.

PY - 2020/5/4

Y1 - 2020/5/4

N2 - T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.

AB - T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system.

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U2 - 10.1084/jem.20190834

DO - 10.1084/jem.20190834

M3 - Article

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AN - SCOPUS:85081563962

SN - 0022-1007

VL - 217

JO - Journal of Experimental Medicine

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ER -

A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

Abstract

Bibliographical note

ASJC Scopus subject areas

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