CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome

Paola Cura Daball, Monica Sofia Ventura Ferreira, Sandra Ammann, Christian Klemann, Myriam R. Lorenz, Ursula Warthorst, Timothy Ronan Leahy, Niall Conlon, Justin Roche, Pere Soler-Palacín, Marina Garcia-Prat, Ilka Fuchs, Sebastian Fuchs, Fabian Beier, Tim H. Brümmendorf, Carsten Speckmann, Peter Olbrich, Olaf Neth, Klaus Schwarz, Stephan EhlAnne Rensing-Ehl

    Research output: Contribution to journalArticleResearch

    7 Citations (Scopus)

    Abstract

    © 2018 Australasian Society for Immunology Inc. Premature T-cell immunosenescence with CD57+ CD8+ T-cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T-cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57+ CD8+ T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57+ CD8+ T cells from APDS patients were less differentiated with more CD27+ CD28+ effector memory T cells showing increased PD1 and Eomesodermin expression. In addition, transition of naïve to CD57+ CD8+ T cells was not associated with the characteristic telomere shortening. Nevertheless, they showed the increased interferon-gamma secretion, enhanced degranulation and reduced in vitro proliferation typical of senescent CD57+ CD8+ T cells. Thus, hyperactive PI3 kinase signaling favors premature accumulation of a CD57+ CD8+ T-cell population, which shows most functional features of typical senescent T cells, but is different in terms of differentiation and relative telomere shortening. Initial observations indicate that this specific differentiation state may offer the opportunity to revert premature T-cell immunosenescence and its potential contribution to inflammation and immunodeficiency in APDS.
    Original languageEnglish
    Pages (from-to)1060-1071
    JournalImmunology and Cell Biology
    Volume96
    DOIs
    Publication statusPublished - 1 Nov 2018

    Keywords

    • Activated PI3Kdelta syndrome
    • CD57
    • immunodeficiency
    • T-cell differentiation
    • T-cell senescence
    • telomeres

    Fingerprint Dive into the research topics of 'CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome'. Together they form a unique fingerprint.

    Cite this