Direct analysis of thymic function in children with Down's syndrome

Prada Nicole, Nasi Milena, Troiano Leonarda, Roat Erika, Pinti Marcello, Nemes Elisa, Lugli Enrico, Ferraresi Roberta, Ciacci Luigi, Bertoni Davide, Biagioni Ornella, Gibertoni Milena, Cornia Cristina, Meschiari Liviana, Gramazio Elisabetta, Mariotti Mauro, Consolo Ugo, Balli Fiorella, Cossarizza Andrea

Description

Down's syndrome (DS) is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE) in children with DS. Methods We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE, i.e. peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC). Results In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. Conclusions The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects.

Sujets

• Down syndrome
• Thymus
• TREC
• T cell

Informations

• Publié par: biomed
• Publié le: 01 janvier 2005
• Nombre de lectures: 24
• Langue: English

Extrait

Immunity & Ageing

BioMedCentral

Open Access Research Direct analysis of thymic function in children with Down's syndrome †1 †22 2 Nicole Prada, Milena Nasi, Leonarda Troiano, Erika Roat, 2 2 22 3 Marcello Pinti, Elisa Nemes, Enrico Lugli, Roberta Ferraresi, Luigi Ciacci, 3 44 4 Davide Bertoni, Ornella Biagioni, Milena Gibertoni, Cristina Cornia, 4 44 3 Liviana Meschiari, Elisabetta Gramazio, Mauro Mariotti, Ugo Consolo, 5 2 Fiorella Balliand Andrea Cossarizza*

1 2 Address: Dipartimentodi Biopatologia e Metodologie Biomediche, Università di Palermo, via Tukory 211, 90134 Palermo, Italy,Cattedra di 3 Immunologia, Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, via Campi 287, 41100 Modena, Italy,Clinica 4 Odontoiatrica, Università di Modena e Reggio Emilia, via del Pozzo 71, 41100 Modena, Italy,Servizio di Neuropsichiatria Infantile, AUSL 5 Modena, via Cardarelli 45, 41100 Modena, Italy andClinica Pediatrica, Università di Modena e Reggio Emilia, via del Pozzo 71, 41100 Modena, Italy Email: Nicole Prada  [e-mail]; Milena Nasi  [e-mail]; Leonarda Troiano  [e-mail]; Erika Roat  [e-mail]; Marcello Pinti  [e-mail]; Elisa Nemes  [e-mail]; Enrico Lugli  [e-mail]; Roberta Ferraresi  [e-mail]; Luigi Ciacci  [e-mail]; Davide Bertoni  [e-mail]; Ornella Biagioni  [e-mail]; Milena Gibertoni  [e-mail]; Cristina Cornia  [e-mail]; Liviana Meschiari  [e-mail]; Elisabetta Gramazio  [e-mail]; Mauro Mariotti  [e-mail]; Ugo Consolo  [e-mail]; Fiorella Balli  [e-mail]; Andrea Cossarizza*  [e-mail] * Corresponding author†Equal contributors

Published: 16 February 2005Received: 05 February 2005 Accepted: 16 February 2005 Immunity & Ageing2005,2:4 doi:10.1186/1742-4933-2-4 This article is available from: http://www.immunityageing.com/content/2/1/4 © 2005 Prada et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Down's syndromethymusTRECT lymphocytes

Abstract Background:Down's syndrome (DS) is characterized by several immunological defects, especially regarding T cell compartment. DS is considered the best example of accelerated ageing in humans. Direct observations of the thymus have shown that in DS this organ undergoes severe histological and morphological changes. However, no data on its capacity to generate T cells are present in the literature. Here, using a new technology based upon real time PCR, we have investigated the capacity of the thymus to produce and release newly generated T lymphocytes (the so called "recent thymic emigrants", RTE) in children with DS. Methods:We studied 8 children affected by DS, aged 2–7 years, compared with 8 age- and sex-matched healthy controls. Flow cytometry was used to determine different lymphocytes subsets. Real time PCR with the Taqman system was used to quantify the amount of RTE,i.e.peripheral blood lymphocytes that express the T cell receptor rearrangement excision circles (TREC). Results:In comparison with control children, those with DS had a significant lower number of TREC+ peripheral blood cells. Moreover, in DS children but not in controls, a strong negative correlation between age and the levels of TREC+ cells was found. Conclusions:The direct measure of thymic output indicates that the impairment of the organ results in a reduced production of newly generated T cells. This observation could suggest that cytokines able to modulate thymic function, such as interleukins, could be useful to improve the functionality of the organ and to treat the immunodeficiency present in DS subjects.

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