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.
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.
Authors: Francisco J Quintana; Bonny Patel; Ada Yeste; Mukanthu Nyirenda; Jessica Kenison; Roya Rahbari; Dumitru Fetco; Mohammad Hussain; Julia O'Mahony; Sandra Magalhaes; Melissa McGowan; Trina Johnson; Sathy Rajasekharan; Sridar Narayanan; Douglas L Arnold; Howard L Weiner; Brenda Banwell; Amit Bar-Or Journal: Neurology Date: 2014-11-07 Impact factor: 9.910
Authors: Mary E Severin; Priscilla W Lee; Yue Liu; Amanda J Selhorst; Matthew G Gormley; Wei Pei; Yuhong Yang; Mireia Guerau-de-Arellano; Michael K Racke; Amy E Lovett-Racke Journal: Brain Date: 2016-04-28 Impact factor: 13.501
Authors: Nirupama D Verma; Andrew D Lam; Christopher Chiu; Giang T Tran; Bruce M Hall; Suzanne J Hodgkinson Journal: Sci Rep Date: 2021-05-18 Impact factor: 4.379