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 αβ+ T cells, but normal γδ+ T cell numbers compared to HI. Concerning the αβ+ 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.

Additional Metadata
Keywords CD28null, NBS, senescence, sjTREC, T cells
Persistent URL dx.doi.org/10.1007/s10875-016-0363-5, hdl.handle.net/1765/95088
Journal Journal of Clinical Immunology
Meijers, R.W.J, Dzierzanowska-Fangrat, M, Zborowska, M. (Magdalena), Solarska, I. (Iwona), Tielemans, D, van Turnhout, B.A.C. (Bob A. C.), … Langerak, A.W. (2017). Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence. Journal of Clinical Immunology, 37(2), 133–142. doi:10.1007/s10875-016-0363-5