Distinctive T-cell receptor repertoire in paediatric inflammatory multisystem syndrome temporally associated with...

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 infection. 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 proportions 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 severe 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.