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

Cattedra di Immunologia, Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, via Campi 287, 41100 Modena, Italy. .
Immunity & Ageing (Impact Factor: 3.54). 03/2005; 2(1):4. DOI: 10.1186/1742-4933-2-4
Source: PubMed


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.

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).

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.

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.

Download full-text


Available from: Marcello Pinti,
  • Source
    • "In recent years attempts have been made to quantify thymic output by using T-cell receptor excision circle (TREC) content of cells. Lower percentages of TREC positive lymphocytes have been shown in children with DS, which showed an agerelated decrease in contrast to healthy controls [54] [55]. Low TREC content, however, might rather be explained by lower percentage of naı¨ve T-cells in DS, the main cell type containing TRECs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Down syndrome (DS) is the most common chromosomal abnormality among live-born infants. Respiratory tract infections are the most important cause of mortality in individuals with DS at all ages. In recent decades several studies have been performed to elucidate abnormalities of the immune system in DS. However, the influence of the immune system on the occurrence of respiratory tract infections in these children has never been reviewed.
    Microbes and Infection 10/2010; 12(11):799-808. DOI:10.1016/j.micinf.2010.05.007 · 2.86 Impact Factor
  • Source
    • "Down syndrome (DS, trisomy 21) is the most frequent chromosomal abnormality in live births and the most frequent cause of mental retardation. This condition is associated with a number of manifestations including heart defects, type I diabetes mellitus, hypotonia, increased susceptibility to bacterial and viral infections and a precocious development of Alzheimer disease, as well as several defects of the acquired immune response [1] [2] [3] [4]. Neurons from DS subjects display an increased susceptibility to apoptosis [5] [6] [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Different types of cells from subjects with Down syndrome (DS) have an increased susceptibility to cell death. We have studied apoptosis and mitochondrial (mt) membrane potential (DeltaPsi(m)) in peripheral blood mononuclear cells (PBMC) from DS children and age-matched healthy donors after in vitro treatment with apoptogenic molecules, along with mtDNA content. We found that PBMC from DS and healthy controls had a similar tendency to undergo apoptosis and a similar amount of mtDNA. However, in cells from DS subjects, mitochondria showed a higher loss of DeltaPsi(m), underlying the presence of an increasing susceptibility of these organelles to damaging agents.
    FEBS Letters 03/2007; 581(3):521-5. DOI:10.1016/j.febslet.2006.12.058 · 3.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It is well established that the polymorphisms at the 5' of the insulin gene (IDDM2) confers susceptibility to type 1 diabetes, probably by modifying the level of insulin expression in the thymus that in turn influences immunological tolerance to insulin as self-antigen. AIRE is a transcription regulator which controls the expression of many peripheral antigens within the thymus, among them insulin. Results presented here confirm that insulin gene copies from both parental chromosomes are expressed in human thymus and that IDDM2 class III protective alleles are indeed associated with a higher level of insulin message expression. However, differences in insulin mRNA expression among different thymi were far wider than those determined by the class I and class III insulin gene alleles and maintained a clear correlation with AIRE expression. These results confirm the effect of IDDM2 alleles on insulin expression in the thymus, but suggest that the levels of AIRE may exert a stronger influence than IDDM2 alleles themselves.
    Journal of Autoimmunity 01/2006; 25(4):312-8. DOI:10.1016/j.jaut.2005.08.006 · 8.41 Impact Factor
Show more