Yanez, Diana C;
Rowell, Jasmine;
Woodall, Maximillian;
Adams, Stuart;
O'Neill, Lauran;
Mengrelis, Konstantinos;
Lau, Ching-In;
... Crompton, Tessa; + view all
(2025)
Distinctive T-cell receptor repertoire in paediatric inflammatory multisystem syndrome temporally associated with coronavirus disease 2019/multisystem inflammatory syndrome in children patients: possible thymus involvement.
Clinical and Experimental Immunology
, 219
(1)
, Article uxaf027. 10.1093/cei/uxaf027.
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Abstract
During the coronavirus disease 2019 (COVID-19) pandemic a rare new paediatric inflammatory condition (paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS)/MIS-C) was identified which correlated with previous or recent SARS-CoV-2 infec¬tion. PIMS-TS led to severe multiorgan inflammation, suggestive of disruption of central tolerance and thymus function. Here we investigated the possible role of the thymus in paediatric PIMS-TS. We confirmed that human thymus explants can be infected with SARS-CoV-2 in vitro. Comparison of T-cell populations in blood from PIMS-TS patients and age-matched healthy control children showed that although the overall pro¬portions of CD4 and CD8 T-cell populations were decreased in PIMS-TS patients, the proportion of naïve cells in the CD4 population was higher in the PIMS-TS group. In PIMS-TS patients, the number of TREC in Peripheral blood mononuclear cells (PBMC) correlated strongly with the proportion of naïve CD4 and CD8 T cells, whereas this correlation was not present in healthy children. Sequencing rearranged TCRβ and TCRɑ transcripts from FACS-sorted CD4+CD8-CD3+ and CD4-CD8+CD3+ from blood from PIMS-TS, healthy children, and additionally paediatric se¬vere COVID-19 patients showed that while all three groups showed similar diversity and distribution, the repertoire of the PIMS-TS and COVID- 19 groups had distinctive patterns of TCR gene segment usage and VJ combinatorial usage compared to healthy controls (TRBV11-2 × TRBJ2-7, TRBV11-2 × TRBJ1-1, TRBV11-2 × TRBJ2-5, TRBV11-2 × TRBJ2-1; TRBV29-1 × TRBJ2-7, TRBV29-1 × TRBJ1-1 enriched in PIMS-TS; TRBV7-9 × TRBJ1-2, TRAV9-2 × TRAJ30, and TRAV26-1 × TRAJ39 enriched in COVID-19). The non-productive TCR rearrangements in the PIMS-TS group were also enriched for TRBV11-2, and showed bias towards distal (5′TRAV to 3′TRAJ) TCRɑ gene segment usage, suggesting involvement of the thymus in PIMS-TS.
| Type: | Article |
|---|---|
| Title: | Distinctive T-cell receptor repertoire in paediatric inflammatory multisystem syndrome temporally associated with coronavirus disease 2019/multisystem inflammatory syndrome in children patients: possible thymus involvement |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/cei/uxaf027 |
| Publisher version: | https://doi.org/10.1093/cei/uxaf027 |
| Language: | English |
| Additional information: | © The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, PIMS-TS, MIS-C, COVID-19, thymus, TCR repertoire, TREC, POWER-LAW DISTRIBUTIONS, THYMECTOMY, DYNAMICS, STEM |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10218081 |
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