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

被引：24

作者：

Prada N. ^{[1
]}

Nasi M. ^{[2
]}

Troiano L. ^{[2
]}

Roat E. ^{[2
]}

Pinti M. ^{[2
]}

Nemes E. ^{[2
]}

Lugli E. ^{[2
]}

Ferraresi R. ^{[2
]}

Ciacci L. ^{[3
]}

Bertoni D. ^{[3
]}

Biagioni O. ^{[4
]}

Gibertoni M. ^{[4
]}

Cornia C. ^{[4
]}

Meschiari L. ^{[4
]}

Gramazio E. ^{[4
]}

Mariotti M. ^{[4
]}

Consolo U. ^{[3
]}

Balli F. ^{[5
]}

Cossarizza A. ^{[2
]}

机构：

[1] Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, 90134 Palermo

[2] Cattedra di Immunologia, Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, 41100 Modena

[3] Clinica Odontoiatrica, Università de Modena e Reggio Emilia, 41100 Modena

[4] Servizio di Neuropsichiatrica Infantile, AUSL Modena, 41100 Modena

[5] Dipartimento di Clinica Pediatrica, Università de Modena e Reggio Emilia, 41100 Modena

来源：

Immunity & Ageing | / 2卷 / 1期

关键词：

Down's syndrome; T lymphocytes; Thymus; TREC;

D O I：

10.1186/1742-4933-2-4

中图分类号：

学科分类号：

摘要：

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. © 2005 Prada et al; licensee BioMed Central Ltd.

引用

共 26 条

[21]

Hazenberg M.D., Otto S.A., de Pauw E.S., Roelofs H., Fibbe W.E., Hamann D., Miedema F., T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events, Blood, 99, pp. 3449-3453, (2002)

[22]

Poulin J.F., Sylvestre M., Champagne P., Dion M.L., Kettaf N., Dumont A., Lainesse M., Fontaine P., Roy D.C., Perreault C., Sekaly R.P., Cheynier R., Evidence for adequate thymic function but impaired naive Tcell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease, Blood, 102, pp. 4600-4607, (2003)

[23]

Ye P., Kirschner D.E., Kourtis A.P., The thymus during HIV disease: Role in pathogenesis and in immune recovery, Curr HIV Res, 2, pp. 177-183, (2004)

[24]

Mussini C., Pinti M., Borghi V., Nasi M., Amorico G., Monterastelli E., Moretti L., Troiano L., Esposito R., Cossarizza A., Features of 'CD4-exploders', HIV-positive patients with an optimal immune reconstitution after potent antiretroviral therapy, AIDS, 16, pp. 1609-1616, (2002)

[25]

Correa R., Munoz-Fernandez A., Effects of highly active antiretroviral therapy on thymical reconstitution of CD4 T lymphocytes in vertically HIV-infected children, AIDS, 16, pp. 1181-1183, (2002)

[26]

Okamoto Y., Douek D.C., McFarland R.D., Koup R.A., IL-7, the thymus, and naive T cells, Adv Exp Med Biol, 512, pp. 81-90, (2002)

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