Direct analysis of thymic function in children with Down's syndrome - PubMed (original) (raw)

doi: 10.1186/1742-4933-2-4. eCollection 2005.

Milena Nasi # 2, Leonarda Troiano 2, Erika Roat 2, Marcello Pinti 2, Elisa Nemes 2, Enrico Lugli 2, Roberta Ferraresi 2, Luigi Ciacci 3, Davide Bertoni 3, Ornella Biagioni 4, Milena Gibertoni 4, Cristina Cornia 4, Liviana Meschiari 4, Elisabetta Gramazio 4, Mauro Mariotti 4, Ugo Consolo 3, Fiorella Balli 5, Andrea Cossarizza 2

Affiliations

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

Nicole Prada et al. Immun Ageing. 2005.

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.

Keywords: Down's syndrome; T lymphocytes; TREC; thymus.

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Figures

Figure 1

Figure 1

Phenotypic analysis of peripheral blood lymphocytes in patients with Down's syndrome (DS) and healthy subjects. Data are referred to 8 individuals per group. Asterisk indicates a statistically significant difference (p < 0.05).

Figure 2

Figure 2

Representative example of real time PCR for the quantification of TREC in a group of 3 children with Down's syndrome (DS) and in 4 healthy controls (each measure is performed in triplicate). Note how the threshold cycle is different in the two groups.

Figure 3

Figure 3

DS children have less TREC+ lymphocytes than healthy controls, as shown in this box-and-whiskers graphics. The boxes extend from the 25th percentile (x[25]) to the 75th percentile (x[75]) [i.e., the interquartile range (IQ)]; lines inside boxes represent median values. Lines emerging from boxes (i.e., the whiskers) extend to the upper and lower adjacent values. The upper adjacent value is defined as the largest data point ≤x[75]+1.5xIQ, and the lower adjacent value is defined as the smallest data point ≥x[25]-1.5xIQ. Note that no outliers are present in the two groups.

Figure 4

Figure 4

Correlation between age and TREC levels in DS (squares) and control (triangles) children. In the year range 2–8, the correlation was significant in DS but not in control children.

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