Age-dependent variations in circulating Tfh and Tfr cells following SARS-CoV-2 infection
Andrey G Velichkov1, Rumyana I Susurkova1, Angelina I Trifonova2
1Laboratory of Reproductive OMICs Technologies Institute of Biology and Immunology of Reproduction "Acad. Kiril Bratanov", 1113 Sofia, Bulgaria.
Insights
COVID-19 immune responses differ by age. Paediatric patients show distinct T follicular helper (Tfh) and T follicular regulatory (Tfr) cell profiles compared to adults, impacting SARS-CoV-2 infection outcomes.
Area of Science:
- Immunology
- Virology
- Paediatric Medicine
Background:
- COVID-19 clinical presentations vary between children and adults.
- T follicular helper (Tfh) and T follicular regulatory (Tfr) cells play roles in adaptive immunity and antibody production.
- Understanding age-specific immune cell dynamics is crucial for explaining clinical differences in SARS-CoV-2 infection.
Purpose of the Study:
- To investigate age-dependent differences in circulating Tfh and Tfr cells in paediatric and adult individuals post-SARS-CoV-2 infection.
- To correlate these immune cell profiles with specific anti-SARS-CoV-2 antibody and T cell responses.
- To explore how these immune differences may underlie observed clinical variations in COVID-19.
Main Methods:
- Flow cytometry was used to analyze circulating Tfh (CXCR5+CD4+) and Tfr (CXCR5+CD4+FOXP3+) cells.
- Enzyme-linked fluorescent assay measured anti-Spike RBD IgG antibodies.
- In vitro cell-based assay assessed neutralizing antibody activity, and ELISpot assay evaluated IFN-γ T cell responses.
Main Results:
- Paediatric patients exhibited a higher percentage of cTfr cells and a lower percentage of cTfh cells, resulting in a decreased cTfh/cTfr ratio compared to adults.
- Increased proportions of ICOS- and HLA-DR-expressing Tfh and Tfr cells were noted in children, correlating with higher antibody response rates.
- Adults showed a higher percentage of IFN-γ-producing T cells in response to viral peptides, with plasmablast presence correlating to the cTfh/cTfr ratio.
Conclusions:
- Circulating Tfh and Tfr cells display significant age-specific differences in the context of SARS-CoV-2 infection.
- These distinct immune cell profiles in children and adults may contribute to the immunologic basis of differential clinical manifestations of COVID-19.
- While antibody neutralizing capacity was similar, T cell responses and regulatory cell ratios varied significantly by age.
Abstract:
Studies of the COVID-19 pandemic revealed differences in the clinical course between paediatric and adult patients. In-depth research on whether T follicular cells support these observations is still ongoing. Circulating Tfh and Tfr cells were examined to identify specific immune responses in paediatric and adult individuals who recovered from asymptomatic to mild SARS-CoV-2 infection. Circulating Tfh and Tfr cells were evaluated by flow cytometry. To evaluate specific anti-SARS-CoV-2 immune responses, anti-Spike RBD IgG antibodies were measured by an enzyme-linked fluorescent assay, anti-Spike neutralizing activity - by an in vitro cell-based assay, and IFN-γ T cell responses were evaluated via ELISpot assay. Age-specific differences in the profiles of the CXCR5+CD4+ T cells that distinguish them from CXCR5- counterparts were detected. An increased percentage of cTfr cells and decreased percentage of cTfh cells was observed in the paediatric group, which resulted in a decreased cTfh/cTfr ratio. Increased proportions of ICOS- and HLA-DR-expressing cTfh and cTfr cells were also observed, consistent with the high proportion of antibody-responders among children. In contrast, a greater percentage of adults than children exhibited IFN-γ-positive T cells in response to the four viral peptides. In adult responders, a good correlation was found between the presence of plasmablasts and the cTfh/cTfr ratio. Antibody neutralizing capacity did not differ between children and adults. Circulating Tfh and Tfr cells exhibit specific age-dependent differences, which may contribute to the immunologic background of the clinical symptoms of SARS-CoV-2 infection.
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