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Updated: Jun 4, 2026
Isolation and Transplantation of Different Aged Murine Thymic Grafts.
Published on: May 13, 2015
Decreased thymic output accounts for decreased naive T cell numbers in children with Down syndrome
Beatrijs L P Bloemers1, Louis Bont, Roel A de Weger
1Department of Paediatric Infectious Diseases and Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Insights
Children with Down syndrome (DS) have fewer naive T cells due to reduced thymic output. Peripheral T cell generation and survival are not impaired, indicating the thymus is the primary issue in DS immune deficiency.
Area of Science:
- Immunology
- Developmental Biology
- Genetics
Background:
- Children with Down syndrome (DS) exhibit reduced naive T cell counts and impaired thymus function.
- Peripheral T cell proliferation is crucial for maintaining naive T cell numbers in healthy children.
Purpose of the Study:
- To investigate the causes of diminished naive T cell numbers in children with Down syndrome.
- To differentiate between reduced thymic output and peripheral T cell dynamics as the cause.
Main Methods:
- Quantification of signal joint TCR excision circles (sjTREC) as a measure of recent thymic emigrants.
- Analysis of recent thymic emigrants (CD3+CD45RA+CD62L+ T cells) and naive T cell apoptosis and activation markers.
- Assessment of naive T cell proliferation in response to IL-7 and Ki-67 expression.
Main Results:
- Children with DS had significantly lower sjTREC levels compared to age-matched controls.
- Reduced frequencies of recent thymic emigrants (PTC7+) were observed in DS, suggesting decreased thymic output.
- Naive T cells in DS showed normal apoptosis, activation, and proliferation rates, with no evidence of defective peripheral generation.
Conclusions:
- The primary cause of low naive T cell numbers in Down syndrome is reduced thymic output.
- Peripheral T cell generation and survival are not significantly impaired in children with DS.
- Therapeutic strategies for DS should focus on enhancing thymic function to restore naive T cell populations.
Abstract:
Children with Down syndrome (DS) have low numbers of naive T cells and abnormal thymus development and function. Because next to thymic production, peripheral proliferation greatly contributes to naive T cell generation in healthy children, we examined the cause of reduced naive T cell numbers in children with DS. Compared with aged matched controls, the total number of signal joint TCR excision circles (sjTREC) per ml blood was reduced in DS. Reduced frequencies and absolute numbers of protein tyrosine kinase 7-positive recent thymic emigrants, but similar levels of naive T cell apoptosis and Ag-driven activation in DS, suggested that reduced thymic output and not increased peripheral loss of naive T cells caused the reduced sjTREC numbers. We found no support for defective peripheral generation of naive T cells in DS. In DS the naive T cells responded to IL-7 and, based on Ki-67 expression, had similar proliferation rates as in healthy controls. sjTREC content per naive CD8(+) T cells was not increased, but even decreased, pointing to increased survival or peripheral generation of naive T cells in DS. In conclusion, we show in this study that reduced thymic output, but not reduced peripheral generation nor increased loss of naive T cells, results in the low naive T cell numbers found in DS.
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