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Quantitative, Phenotypical, and Functional Characterization of Cellular Immunity in Children and Adolescents With
Justine Schoch1, Tilman R Rohrer2, Michael Kaestner3
1Departments of Transplant and Infection Immunology.
Insights
Individuals with Down syndrome exhibit altered T-cell populations but can effectively mount antigen-specific T-cell responses, similar to controls. Higher frequencies of effector T cells may be needed for pathogen control in Down syndrome.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Down syndrome is associated with increased infections and autoimmune disorders, indicating immune system abnormalities.
- While B cell and antibody roles are understood, T cell function in Down syndrome remains less clear.
Purpose of the Study:
- To investigate T cell subpopulations and effector T cell functionality in children and adolescents with Down syndrome.
- To compare T cell responses to polyclonal and pathogen-specific stimulation between individuals with and without Down syndrome.
Main Methods:
- Quantified lymphocyte subpopulations in 40 individuals with Down syndrome and 51 controls.
- Analyzed antigen-specific effector T cell phenotype and function using flow cytometry after stimulation with VZV and CMV.
- Correlated results with immunoglobulin G responses.
Main Results:
- T-cell subpopulations showed altered percentages and increased expression of the inhibitory receptor PD-1 in Down syndrome.
- Effector CD4+ T-cell frequencies were higher in Down syndrome, with similar inhibitory receptor expression and cytokine profiles compared to controls.
- Pathogen-specific immunity was age-appropriate, with correlations between cellular and humoral immunity for CMV and higher VZV-specific T-cell responses in VZV IgG-positive individuals with Down syndrome.
Conclusions:
- Individuals with Down syndrome demonstrate comparable effector T-cell phenotype and functionality to controls, despite altered lymphocyte subpopulations.
- Higher frequencies of effector T cells might be necessary for effective pathogen control in individuals with Down syndrome.
Background:
Infections and autoimmune disorders are more frequent in Down syndrome, suggesting abnormality of adaptive immunity. Although the role of B cells and antibodies is well characterized, knowledge regarding T cells is limited.
Methods:
Lymphocyte subpopulations of 40 children and adolescents with Down syndrome and 51 controls were quantified, and phenotype and functionality of antigen-specific effector T cells were analyzed with flow cytometry after polyclonal and pathogen-specific stimulation (with varicella-zoster virus [VZV] and cytomegalovirus [CMV]). Results were correlated with immunoglobulin (Ig) G responses.
Results:
Apart from general alterations in the percentage of lymphocytes, regulatory T cells, and T-helper 1 and 17 cells, all major T-cell subpopulations showed higher expression of the inhibitory receptor PD-1. Polyclonally stimulated effector CD4+ T-cell frequencies were significantly higher in subjects with Down syndrome, whereas their inhibitory receptor expression (programmed cell death 1 [PD-1] and cytotoxic T-lymphocyte antigen 4 [CTLA-4]) was similar to that of controls and cytokine expression profiles were only marginally altered. Pathogen-specific immunity showed age-appropriate levels of endemic infection, with correlation of CMV-specific cellular and humoral immunity in all subjects. Among VZV IgG-positive individuals, a higher percentage of VZV-specific T-cell-positive subjects was seen in those with Down syndrome.
Conclusions:
Despite alterations in lymphocyte subpopulations, individuals with Down syndrome can mount effector T-cell responses with similar phenotype and functionality as controls but may require higher effector T-cell frequencies to ensure pathogen control.
