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Peer-reviewedCC BYEuropean journal of immunology

Increased Output of Recent Thymic Emigrants Contributes to Reconstitution of T‐Cell Pool During Recovery From COVID‐19

  • Xiaobo Huang1,2
  • Suvi T Jokiranta1,2
  • Kirsten Nowlan1,2
  • Ngoc Anh Nguyen1,2
  • Nelli Heikkilä1,2
  • Lauriina Tola1,2
  • Anu Kantele3
  • Pirkka T Pekkarinen2,4
  • Johanna Hästbacka5
  • Olli Vapalahti6,7,8
  • Santtu Heinonen9
  • Juuso Paajanen10
2 more authors
  • Tomas Strandin6
  • Eliisa Kekäläinen1,2,7,11
11 affiliations
  1. 1Translational Immunology Research Program, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  2. 2Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
  3. 3Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  4. 4Division of Intensive Care Medicine, Department of Anaesthesiology and Intensive Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  5. 5Faculty of Medicine and Health Technology, Tampere University Hospital, Wellbeing Services County of Pirkanmaa and Tampere University, Tampere, Finland.
  6. 6Department of Virology, Medicum, Viral Zoonoses Research Unit, University of Helsinki, Helsinki, Finland.
  7. 7HUSLAB Clinical Microbiology, Division of Virology and Immunology, HUS Diagnostic Center, Helsinki, Finland.
  8. 8Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
  9. 9New Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  10. 10Department of Pulmonology, University of Helsinki and Helsinki University Hospital, Meilahti Hospital, Helsinki, Finland.
  11. 11Helsinki Institute of Life Sciences, HiLIFE, University of Helsinki, Helsinki, Finland.
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Abstract

Acute coronavirus disease 2019 (COVID-19) causes marked T-cell lymphopenia, with recovery potentially driven by peripheral proliferation or increased thymic output of recent thymic emigrants (RTEs). We examined the relative contribution of these mechanisms by analyzing naïve T-cell and RTE dynamics in 63 patients sampled at 1-3 timepoints during and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Overall frequencies of naïve CD4+ and CD8+ T cells remained stable during convalescence. In a female-biased subcohort with paired samples, CD31+ CD4+ and CD21+ CD8+ RTE-enriched subset frequencies increased from acute to late convalescence (LC) stage. Across the full cohort, a significant increase was confirmed for CD21+ CD8+ RTE-enriched subsets. PD-1 and Ki67 expression did not explain this rise, indicating enhancement of thymic output despite the cohort's high median age. Patients requiring ICU care had lower CD31+ CD4+ RTE-enriched subset frequencies in LC compared with non-ICU cases. Regression coefficient modeling identified male sex as a negative predictor of CD31+ CD4+ RTE-enriched subset frequency, potentially contributing to distinct CD31+ CD4+ and CD21+ CD8+ RTE-enriched subset kinetics. Together, these findings suggest that de novo thymic output, particularly CD21+ CD8+ RTE-enriched subset, contributes to T-cell reconstitution after COVID-19 and may influence susceptibility to post-infectious immune dysregulation.

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Cite

BibTeXRIS
BibTeX
@article{huang2026increased,
  title = {{Increased Output of Recent Thymic Emigrants Contributes to Reconstitution of T‐Cell Pool During Recovery From COVID‐19}},
  author = {Xiaobo Huang and Suvi T Jokiranta and Kirsten Nowlan and Ngoc Anh Nguyen and Nelli Heikkilä and Lauriina Tola and Anu Kantele and Pirkka T Pekkarinen and Johanna Hästbacka and Olli Vapalahti and Santtu Heinonen and Juuso Paajanen and Tomas Strandin and Eliisa Kekäläinen},
  journal = {European journal of immunology},
  year = {2026},
  month = oct,
  doi = {10.1002/eji.70303},
  url = {https://europepmc.org/article/PMC/PMC13718309},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Increased Output of Recent Thymic Emigrants Contributes to Reconstitution of T‐Cell Pool During Recovery From COVID‐19
AU  - Xiaobo Huang
AU  - Suvi T Jokiranta
AU  - Kirsten Nowlan
AU  - Ngoc Anh Nguyen
AU  - Nelli Heikkilä
AU  - Lauriina Tola
AU  - Anu Kantele
AU  - Pirkka T Pekkarinen
AU  - Johanna Hästbacka
AU  - Olli Vapalahti
AU  - Santtu Heinonen
AU  - Juuso Paajanen
AU  - Tomas Strandin
AU  - Eliisa Kekäläinen
PY  - 2026
DA  - 2026/10/01
JO  - European journal of immunology
DO  - 10.1002/eji.70303
UR  - https://europepmc.org/article/PMC/PMC13718309
AB  - Acute coronavirus disease 2019 (COVID-19) causes marked T-cell lymphopenia, with recovery potentially driven by peripheral proliferation or increased thymic output of recent thymic emigrants (RTEs). We examined the relative contribution of these mechanisms by analyzing naïve T-cell and RTE dynamics in 63 patients sampled at 1-3 timepoints during and after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Overall frequencies of naïve CD4+ and CD8+ T cells remained stable during convalescence. In a female-biased subcohort with paired samples, CD31+ CD4+ and CD21+ CD8+ RTE-enriched subset frequencies increased from acute to late convalescence (LC) stage. Across the full cohort, a significant increase was confirmed for CD21+ CD8+ RTE-enriched subsets. PD-1 and Ki67 expression did not explain this rise, indicating enhancement of thymic output despite the cohort's high median age. Patients requiring ICU care had lower CD31+ CD4+ RTE-enriched subset frequencies in LC compared with non-ICU cases. Regression coefficient modeling identified male sex as a negative predictor of CD31+ CD4+ RTE-enriched subset frequency, potentially contributing to distinct CD31+ CD4+ and CD21+ CD8+ RTE-enriched subset kinetics. Together, these findings suggest that de novo thymic output, particularly CD21+ CD8+ RTE-enriched subset, contributes to T-cell reconstitution after COVID-19 and may influence susceptibility to post-infectious immune dysregulation.
SN  - 0014-2980
SN  - 1521-4141
ER  -