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
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
收藏
相关论文
共 26 条
[1]  
Epstein C.J., Down Syndrome (Trisomy 21), The Metabolic and Molecular Bases of Inherited Disease, pp. 749-794, (1995)
[2]  
Cossarizza A., Monti D., Montagnani G., Forabosco A., Dagna-Bricarelli F., Franceschi C., Fetal thymic differentiation in Down's syndrome, Thymus, 14, pp. 163-170, (1989)
[3]  
Cossarizza A., Monti D., Dagna-Bricarelli F., Montagnani G., Franceschi C., LAK activity is inducible in blood mononuclear cells from human fetus, Immunol Lett, 24, pp. 137-140, (1990)
[4]  
Cossarizza A., Monti D., Montagnani G., Ortolani C., Masi M., Zannotti M., Franceschi C., Precocious aging of the immune system in Down's syndrome: Alterations of B-lymphocytes, T-lymphocyte subsets and of cells with NK markers, Am J Med Genet Suppl, 7, pp. 213-218, (1990)
[5]  
Franceschi C., Monti D., Cossarizza A., Fagnoni F., Passeri G., Sansoni P., Aging, longevity, and cancer: Studies in Down's syndrome and centenarians, Ann N Y Acad Sci, 621, pp. 428-440, (1991)
[6]  
Cossarizza A., Ortolani C., Forti E., Montagnani G., Paganelli R., Zannotti M., Marini M., Monti D., Franceschi C., Age-related expansion of functionally inefficient cells with markers of NK activity in Down's syndrome, Blood, 77, pp. 1263-1270, (1991)
[7]  
Park E., Alberti J., Mehta P., Dalton A., Sersen E., Schuller-Levis G., Partial impairment of immune functions in peripheral blood leukocytes from aged men with Down's syndrome, Clin Immunol, 95, pp. 62-69, (2000)
[8]  
Cuadrado E., Barrena M.J., Immune dysfunction in Down's syndrome: Primary immune deficiency or early senescence of the immune system?, Clin Immunol Immunopathol, 78, pp. 209-214, (1996)
[9]  
Larocca L.M., Piantelli M., Valitutti S., Castellino F., Maggiano N., Musiani P., Alterations in thymocyte subpopulations in Down's syndrome (trisomy 21), Clin Immunol Immunopathol, 49, pp. 175-186, (1988)
[10]  
Douek D.C., McFarland R.D., Keiser P.H., Gage E.A., Massey J.M., Haynes B.F., Polis M.A., Haase A.T., Feinberg M.B., Sullivan J.L., Jamieson B.D., Zack J.A., Picker L.J., Koup R.A., Changes in thymic function with age and during the treatment of HIV infection, Nature, 396, pp. 690-695, (1998)