Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95.
Abstract
Ataxia-telangiectasia (A-T) is a rare neurodegenerative immunodeficiency disorder caused by mutations in the ataxia telangiectasia mutated gene. Patients commonly have lymphopenia and Ig-production abnormalities. We used multicolor flow cytometry and IL-7 ELISA to investigate the effect of A-T and age on the proportions of major lymphocyte subsets and their pattern of CD95 expression in relation to IL-7 levels in 15 classical A-T patients. We also analyzed the sensitivity of T cells from four classical A-T patients to CD95-mediated apoptosis using TUNEL and caspase-activation assays. Our results confirmed lymphopenia and a deficiency in naive T and B cells in A-T patients. In contrast to controls, the proportions of naive and memory T and B cell subsets in A-T patients did not vary in relation to age. There was no evidence of a deficiency in plasma IL-7 or IL-7R expression, and IL-7 concentration correlated positively with CD95 expression on CD4+ T cells. CD95 expression on unstimulated A-T lymphocytes was high, and the apoptotic sensitivity of activated naive and central memory T cells was increased. These findings show that the immunodeficiency in A-T patients may be described as congenitally aged and is not progressive. The naive cell deficiency is not related to a deficiency in IL-7 or its receptor. However, IL-7 may upregulate CD95 on A-T lymphocytes. High CD95 expression and increased apoptotic sensitivity of activated naive and central memory T cells may result in an increased level of CD95-mediated apoptosis, which could contribute to the congenital lymphopenia in A-T.
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Progeroid syndromes, in which affected individuals begin aging during the second decade of life, share the co-occurrence of deficient immunity and premature age-related morbidities.
“The co-occurrence of deficient immunity and prematurity of age-related morbidities extends to the progeroid syndromes, in which affected individuals begin aging during the second decade of life [66–68].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [67]
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- Authors
- Carney, E. F., Srinivasan, V., Moss, P. A., & Taylor, A. M.
- Affiliations
- University of Birmingham (GB)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-07-01
- Volume
- 189
- Issue
- 1
- Pages
- 261-268
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1932187564
- Cited by
- 26
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 1 · 2014: 3 · 2013: 3
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ataxia telangiectasia, Fas, immunodeficiency, lymphopenia, naive T cells, central memory T cells, IL-7, IL-7 receptor, T cell apoptosis, B cells, plasma cytokines
- MeSH terms
- Adolescent, Adult, Aging, Ataxia Telangiectasia, Cells, Cultured, Child, Female, Humans, Infant, Lymphopenia, Male, Up-Regulation, Apoptosis, fas Receptor, Young Adult
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