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T-cell homeostasis in pediatric multiple sclerosis: Old cells in young patients.
Balint B, Haas J, Schwarz A, Jarius S, Fürwentsches A, Engelhardt K, Bussmann C, Ebinger F, Fritzsching B, Paul F, Seidel U, Vlaho S, Huppke P, Gärtner J, Wildemann B.
Neurology. 2013 Aug 27;81(9):784-792.
To assess pediatric patients with multiple sclerosis (MS) for early signs of homeostatic and functional abnormalities in conventional (Tcon) and regulatory T cells (Treg).
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).
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.
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.