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

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Author(s): 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

Journal: Immunity & Ageing
ISSN 1742-4933

Volume: 2;
Issue: 1;
Start page: 4;
Date: 2005;
Original page

Keywords: Down's syndrome | thymus | TREC | T lymphocytes

ABSTRACT
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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