Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome

Erika Roat, Nicole Prada, Enrico Lugli, Milena Nasi, Roberta Ferraresi, Leonarda Troiano, Chiara Giovenzana, Marcello Pinti, Ornella Biagioni, Mauro Mariotti, Angelo Di Iorio, Ugo Consolo, Fiorella Balli, Andrea Cossarizza

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Abstract

Down syndrome (DS), the most common chromosomal abnormality in humans, is characterized by precocious immunologic aging that results, among other things, in alterations of B and T lymphocyte subsets and natural killer cells, defective phagocytosis, and chemotaxis of polymorphonuclear leukocytes. We studied 30 children affected by DS, compared them to 29 healthy controls, and evaluated the functionality of the thymus (by measuring the amount of lymphocytes that express the signal-joint T cell receptor rearrangement excision circles [sj-TREC+]), the plasma levels of interleukin (IL)-7 and IL-15, the proliferative T cell response to these cytokines, the expression of the α chain of the IL-7 receptor (CD127), the extrathymic differentiation of T lymphocytes, and the presence of natural regulatory T cells (Tregs) in peripheral blood. We found that DS children had a significantly lower number of sj-TREC+ lymphocytes, the levels of which were strongly correlated with age. We found higher plasma levels of IL-7 and IL-15 than in healthy controls, and a higher proliferative T cell response to IL-15. DS children also showed a lower percentage of CD4+ cells and profound alterations of T cell differentiation, along with increased amount of Tregs and of cells expressing markers of apoptosis. We can thus hypothesize that the precocious thymic involution occurring in DS is mirrored by a high production of IL-7 and IL-15, which is crucial for cell survival and proliferation. The complex alterations present in the periphery are likely the result of a compensatory mechanism: the overproduction of homeostatic cytokines could be a reaction to the impaired intrathymic production of T lymphocytes and/or to the expansion of Treg in the periphery, and could be required to allow the survival of T cells.

Original languageEnglish
Pages (from-to)573-583
Number of pages11
JournalRejuvenation Research
Volume11
Issue number3
DOIs
Publication statusPublished - Jun 1 2008

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Regulatory T-Lymphocytes
Down Syndrome
Interleukin-15
Cytokines
T-Lymphocytes
Interleukin-7
Interleukin-7 Receptors
Lymphocytes
B-Lymphocyte Subsets
Cytophagocytosis
T-Lymphocyte Subsets
Chemotaxis
T-Cell Antigen Receptor
Chromosome Aberrations
Natural Killer Cells
Thymus Gland
Cell Differentiation
Cell Survival
Neutrophils
Joints

ASJC Scopus subject areas

  • Ageing

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Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome. / Roat, Erika; Prada, Nicole; Lugli, Enrico; Nasi, Milena; Ferraresi, Roberta; Troiano, Leonarda; Giovenzana, Chiara; Pinti, Marcello; Biagioni, Ornella; Mariotti, Mauro; Di Iorio, Angelo; Consolo, Ugo; Balli, Fiorella; Cossarizza, Andrea.

In: Rejuvenation Research, Vol. 11, No. 3, 01.06.2008, p. 573-583.

Research output: Contribution to journalArticle

Roat, E, Prada, N, Lugli, E, Nasi, M, Ferraresi, R, Troiano, L, Giovenzana, C, Pinti, M, Biagioni, O, Mariotti, M, Di Iorio, A, Consolo, U, Balli, F & Cossarizza, A 2008, 'Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome', Rejuvenation Research, vol. 11, no. 3, pp. 573-583. https://doi.org/10.1089/rej.2007.0648
Roat, Erika ; Prada, Nicole ; Lugli, Enrico ; Nasi, Milena ; Ferraresi, Roberta ; Troiano, Leonarda ; Giovenzana, Chiara ; Pinti, Marcello ; Biagioni, Ornella ; Mariotti, Mauro ; Di Iorio, Angelo ; Consolo, Ugo ; Balli, Fiorella ; Cossarizza, Andrea. / Homeostatic cytokines and expansion of regulatory T cells accompany thymic impairment in children with Down syndrome. In: Rejuvenation Research. 2008 ; Vol. 11, No. 3. pp. 573-583.
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AU - Troiano, Leonarda

AU - Giovenzana, Chiara

AU - Pinti, Marcello

AU - Biagioni, Ornella

AU - Mariotti, Mauro

AU - Di Iorio, Angelo

AU - Consolo, Ugo

AU - Balli, Fiorella

AU - Cossarizza, Andrea

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N2 - Down syndrome (DS), the most common chromosomal abnormality in humans, is characterized by precocious immunologic aging that results, among other things, in alterations of B and T lymphocyte subsets and natural killer cells, defective phagocytosis, and chemotaxis of polymorphonuclear leukocytes. We studied 30 children affected by DS, compared them to 29 healthy controls, and evaluated the functionality of the thymus (by measuring the amount of lymphocytes that express the signal-joint T cell receptor rearrangement excision circles [sj-TREC+]), the plasma levels of interleukin (IL)-7 and IL-15, the proliferative T cell response to these cytokines, the expression of the α chain of the IL-7 receptor (CD127), the extrathymic differentiation of T lymphocytes, and the presence of natural regulatory T cells (Tregs) in peripheral blood. We found that DS children had a significantly lower number of sj-TREC+ lymphocytes, the levels of which were strongly correlated with age. We found higher plasma levels of IL-7 and IL-15 than in healthy controls, and a higher proliferative T cell response to IL-15. DS children also showed a lower percentage of CD4+ cells and profound alterations of T cell differentiation, along with increased amount of Tregs and of cells expressing markers of apoptosis. We can thus hypothesize that the precocious thymic involution occurring in DS is mirrored by a high production of IL-7 and IL-15, which is crucial for cell survival and proliferation. The complex alterations present in the periphery are likely the result of a compensatory mechanism: the overproduction of homeostatic cytokines could be a reaction to the impaired intrathymic production of T lymphocytes and/or to the expansion of Treg in the periphery, and could be required to allow the survival of T cells.

AB - Down syndrome (DS), the most common chromosomal abnormality in humans, is characterized by precocious immunologic aging that results, among other things, in alterations of B and T lymphocyte subsets and natural killer cells, defective phagocytosis, and chemotaxis of polymorphonuclear leukocytes. We studied 30 children affected by DS, compared them to 29 healthy controls, and evaluated the functionality of the thymus (by measuring the amount of lymphocytes that express the signal-joint T cell receptor rearrangement excision circles [sj-TREC+]), the plasma levels of interleukin (IL)-7 and IL-15, the proliferative T cell response to these cytokines, the expression of the α chain of the IL-7 receptor (CD127), the extrathymic differentiation of T lymphocytes, and the presence of natural regulatory T cells (Tregs) in peripheral blood. We found that DS children had a significantly lower number of sj-TREC+ lymphocytes, the levels of which were strongly correlated with age. We found higher plasma levels of IL-7 and IL-15 than in healthy controls, and a higher proliferative T cell response to IL-15. DS children also showed a lower percentage of CD4+ cells and profound alterations of T cell differentiation, along with increased amount of Tregs and of cells expressing markers of apoptosis. We can thus hypothesize that the precocious thymic involution occurring in DS is mirrored by a high production of IL-7 and IL-15, which is crucial for cell survival and proliferation. The complex alterations present in the periphery are likely the result of a compensatory mechanism: the overproduction of homeostatic cytokines could be a reaction to the impaired intrathymic production of T lymphocytes and/or to the expansion of Treg in the periphery, and could be required to allow the survival of T cells.

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