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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Elevated regulatory T cells in pediatric patients recovering from multisystem inflammatory syndrome (MIS-C) are
Isabela Silva-Avelar1, Bruna Danielly Santos-Silva1, Yingying Zheng1
1Departamento de Pediatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Insights
Children recovering from COVID-19 exhibit altered regulatory T cell (Treg) profiles, with Multisystem Inflammatory Syndrome in Children (MIS-C) patients showing higher Treg counts and a temporary immunosuppressive state. These immune changes normalize approximately one year post-infection.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Post-COVID Conditions
Background:
- Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe post-COVID-19 condition.
- Regulatory T cells (Tregs) play a crucial role in modulating immune responses during inflammation.
Purpose of the Study:
- To investigate the Treg cell profile in pediatric patients during recovery from COVID-19.
- To compare Treg cell populations at two distinct convalescence time points (2-8 months and 10-15 months post-infection).
Main Methods:
- Prospective cohort study involving COVID-19 (CV) and MIS-C (MV) convalescent groups, plus a control group.
- Analysis of Treg phenotypes and cytokine profiles (IL-6, IL-8, IL-12, IL-1β, TNF-α, IL-10, TGF-β) using flow cytometry and ELISA.
- Participants were unvaccinated children aged 2-18 years with confirmed SARS-CoV-2 infection.
Main Results:
- COVID-19 and MIS-C groups initially showed reduced inflammatory cytokines (IL-1β, IL-8, IL-12, TNF-α), which normalized by the second visit.
- MIS-C patients (MV1) exhibited higher Treg cell numbers, including CD45RA+ and CTLA-4+ subpopulations, compared to COVID-19 patients (CV1).
- The Foxp3/CD45RA ratio was significantly higher in COVID-19 patients compared to controls and lower in MIS-C patients at the second visit.
Conclusions:
- Pediatric COVID-19 recovery is associated with dynamic changes in Treg cell populations, linked to disease severity.
- MIS-C patients experience a more pronounced temporary immunosuppressive state with elevated Treg counts, which gradually resolves over a year.
- Treg cell profiling offers insights into immune recovery trajectories following COVID-19 and MIS-C in children.
Background:
Children can present a severe post-COVID-19 condition called Multisystem Inflammatory Syndrome in Children (MIS-C) and regulatory T cells (Tregs) can regulate the immune response during the inflammatory process, serving as an important tool for controlling the immune response.
Objective:
To analyze the profile of Tregs in pediatric patients recovering from COVID-19 at two time points: between 2 and 8 months post-infection (visit 1) and between 10 and 15 months post-infection (visit 2).
Methods:
This prospective cohort study included a convenience sample divided into two groups: CV1 (COVID-19, n = 67) and MV1 (MIS-C convalescents, n = 9) at visit 1, and CV2 (n = 42) and MV2 (n = 8) at visit 2. Participants were previously healthy or had pre-existing chronic conditions, diagnosed with COVID-19 between 2020 and 2021, unvaccinated, aged 2-18 years, and had confirmed SARS-CoV-2 infection. A control group of 70 individuals without COVID-19 was included using the same criteria. Treg cell phenotypes and cytokines (IL-6, IL-8, IL-12, IL-1β, TNF-α, IL-10) were analyzed using flow cytometry, and TGF-β by ELISA.
Results:
The study found that the COVID-19 (CV1, CV2) and control (Ct) groups were matched by age, sex, and comorbidities, while the MIS-C groups (MV1, MV2) mostly included previously healthy individuals. Both CV1 and MV1 groups had reduced levels of IL-1β, IL-8, IL-12, and TNF-α, which normalized by visit 2, indicating a gradual recovery from the temporary immunosuppressive state. The MV1 group had higher Treg cell numbers, including CD45RA+ and CTLA-4+ subpopulations, compared to the CV1 group. CD45RA expression was lower in CV1 and MV1, but the Foxp3/CD45RA ratio was significantly higher in CV1 compared to the controls and lower in MV2 compared to MV1 and CV2. MV1 also had higher Treg counts compared to healthy and immunosuppressed individuals from both the CV1 and control groups.
Conclusion:
Children recovering from COVID-19 showed changes in regulatory T cell populations associated with disease severity. Those who developed MIS-C had higher Treg cell counts and a temporary immunosuppressive state that persisted in the early convalescence period, normalizing around a year after infection.
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