Accelerated Maturation, Exhaustion, and Senescence of T cells in 22q11.2 Deletion Syndrome

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F22%3A10433200" target="_blank" >RIV/00216208:11110/22:10433200 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/22:10433200 RIV/00064203:_____/22:10433200 RIV/00064190:_____/21:N0000019

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1Xo89BfOC9" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=1Xo89BfOC9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s10875-021-01154-9" target="_blank" >10.1007/s10875-021-01154-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Accelerated Maturation, Exhaustion, and Senescence of T cells in 22q11.2 Deletion Syndrome

Popis výsledku v původním jazyce

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 &lt; 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.

Název v anglickém jazyce

Accelerated Maturation, Exhaustion, and Senescence of T cells in 22q11.2 Deletion Syndrome

Popis výsledku anglicky

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 &lt; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Clinical Immunology

ISSN

0271-9142

e-ISSN

1573-2592

Svazek periodika

42

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

274-285

Kód UT WoS článku

000712787300001

EID výsledku v databázi Scopus

2-s2.0-85118376306