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- Title
Accelerated Maturation, Exhaustion, and Senescence of T cells in 22q11.2 Deletion Syndrome.
- Authors
Smetanova, Jitka; Milota, Tomas; Rataj, Michal; Bloomfield, Marketa; Sediva, Anna; Klocperk, Adam
- Abstract
Purpose: 22q11.2 deletion syndrome (22q11.2DS) is a primary immunodeficiency characterized chiefly by the hypoplasia of the thymus resulting in T cell lymphopenia, increased susceptibility to infections, and higher risk of autoimmune diseases. The irregular thymic niche of T cell development may contribute to autoimmune and atopic complications, whereas the compensatory mechanism of homeostatic T cell proliferation and continuous immune stimulation may result in T cell senescence and exhaustion, further aggravating the immune system dysregulation. Methods: We used flow cytometry to investigate T cell maturation, delineation, proliferation, activation, and expression of senescence and exhaustion-associated markers (PD1, KLRG1, CD57) in 17 pediatric and adolescent patients with 22q11.2DS and age-matched healthy donors. Results: 22q11.2DS patients aged 0–5 years had fewer naïve but more effector memory T cells with a tendency to approach normal values with increasing age. Young patients in particular had a higher percentage of proliferating T cells and increased expression of PD1, KLRG1, and CD57, as well as cells co-expressing several exhaustion-associated molecules (PD1, KLRG1, Tbet, Eomes, Helios). Additionally, high-risk 22q11.2DS patients with very low numbers of CD4 T cells had significantly higher percentage of Th1 and Th17 T cells, driven in part by higher proportion of mature T cell forms. Conclusion: The low thymic output and accelerated T cell differentiation remain the principal features of 22q11.2DS patient immunity, especially in young patients of < 5 years. Later in life, homeostatic proliferation drives expression of T cell exhaustion and senescence-associated markers, suggesting functional aberrations in addition to numeric T cell deficiency.
- Subjects
DIGEORGE syndrome; 22Q11 deletion syndrome; T cells; CELLULAR aging; DYSTHYMIC disorder; T cell differentiation; T helper cells
- Publication
Journal of Clinical Immunology, 2022, Vol 42, Issue 2, p274
- ISSN
0271-9142
- Publication type
Article
- DOI
10.1007/s10875-021-01154-9