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T-cell homeostasis in pediatric multiple sclerosis: old cells in young patients
Bettina Balint1, Jürgen Haas, Alexander Schwarz
1Division of Molecular Neuroimmunology, Department of Neurology, DZL Junior Group "Airway Inflammation," Translational Lung Research Center, University Hospital Heidelberg, Heidelberg, Germany.
Insights
Pediatric multiple sclerosis (MS) patients show T-cell abnormalities similar to adults, indicating early thymic involution may contribute to disease. Immunomodulatory drugs helped normalize these T-cell changes in pediatric MS (pMS).
Area of Science:
- Immunology
- Neuroimmunology
- Pediatric Autoimmunity
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Understanding T-cell homeostasis in pediatric MS (pMS) is crucial for early diagnosis and treatment.
- Pediatric MS presents unique challenges in T-cell compartment development and function.
Purpose of the Study:
- To investigate early homeostatic and functional abnormalities in conventional (Tcon) and regulatory T cells (Treg) in pediatric MS patients.
- To compare T-cell profiles in pMS with adult MS patients and age-matched controls.
- To assess the impact of immunomodulatory treatments on T-cell alterations in pMS.
Main Methods:
- Cross-sectional study of 30 pMS patients, 26 adult MS patients, and 67 controls.
- Multicolor flow cytometry to analyze peripheral T-cell compartment composition.
- Proliferation assays to assess regulatory T-cell (Treg) function.
Main Results:
- pMS patients exhibited reduced naive T cells and recent thymic emigrants (RTE), with increased memory T cells, mirroring adult MS.
- Dampened suppressive capacities of total Treg were observed in pMS patients.
- These T-cell alterations were attenuated by immunomodulatory drug treatment, similar to adult MS.
- Signs of early thymic involution were evident in pMS, with T-cell subset ratios resembling much older controls.
Conclusions:
- Homeostatic T-cell changes in pMS are comparable to adult-onset MS.
- Early thymic involution may play a role in the pathogenesis of pediatric MS.
- Findings suggest intrinsic defects in thymic T-cell neogenesis could contribute to MS development.
Objective:
To assess pediatric patients with multiple sclerosis (MS) for early signs of homeostatic and functional abnormalities in conventional (Tcon) and regulatory T cells (Treg).
Methods:
We studied the composition of the peripheral T-cell compartment and Treg function in a cross-sectional study with 30 pediatric MS (pMS) patients by multicolor flow cytometry and proliferation assays. Data were compared to those obtained from adult patients (n = 26) and age-matched control donors (n = 67).
Results:
Proportions of naive T cells were 10%-20% higher in children than in adults, reflecting the age-related decline. pMS patients, however, had clearly lower numbers of naive T cells, among them recent thymic emigrants (RTE), whereas percentages of memory T cells were increased. In the Treg compartment, reduced RTE numbers coincided with markedly dampened suppressive capacities of total Treg. These homeostatic changes in circulating T cells precisely paralleled the pattern seen in adult MS. As in adults, treatment with immunomodulatory drugs attenuated these alterations.
Conclusion:
The homeostatic changes detected in the T-cell compartment in pMS are similar to those in adult-onset disease. With ratios between naive and memory T-cell subsets matching those of 20- to 30-years-older controls, signs of early thymic involution are already found in pMS, suggesting that an intrinsic compromise in thymic-dependent T-cell neogenesis might contribute to MS pathogenesis.
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