Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence.
J Clin Immunol
; 37(2): 133-142, 2017 Feb.
Article
em En
| MEDLINE
| ID: mdl-28000062
ABSTRACT
PURPOSE:
The Nijmegen breakage syndrome (NBS) is an inherited genetic disorder characterized by a typical facial appearance, microcephaly, growth retardation, immunodeficiency, and a strong predisposition to malignancies, especially of lymphoid origin. NBS patients have a mutation in the NBN gene which involves the repair of DNA double-strand breaks (DSBs). Here we studied the peripheral T cell compartment of NBS patients with a focus on immunological senescence.METHODS:
The absolute numbers and frequencies of the different T cell subsets were determined in NBS patients from young age till adulthood and compared to age-matched healthy individuals (HI). In addition, we determined the expression of senescent T cell markers and the signal joint T cell receptor excision circles (sjTRECs) content.RESULTS:
Our results demonstrate that NBS patients have reduced T cell numbers. NBS patients showed lower numbers of αß+ T cells, but normal γδ+ T cell numbers compared to HI. Concerning the αß+ T cells, both CD4+ as well as CD8+ T cells were excessively reduced in numbers compared to aged-matched HI. In addition, NBS patients showed higher frequencies of the more differentiated T cells expressing the senescent cell marker CD57 and did not express co-stimulatory molecule CD28. These effects were already present in the youngest age group. Furthermore, NBS patients showed lower sjTREC content in their T cells possibly indicative of a lower thymic output.CONCLUSIONS:
We conclude that circulating T cells from NBS patients show signs of a senescent phenotype which is already present from young age on and which might explain their T cell immune deficiency.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Subpopulações de Linfócitos T
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Senescência Celular
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Contagem de Linfócitos
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Síndrome de Quebra de Nijmegen
Tipo de estudo:
Diagnostic_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
J Clin Immunol
Ano de publicação:
2017
Tipo de documento:
Article