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Immunol Cell Biol ; 96(10): 1060-1071, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29790605


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.

Antígenos CD57/metabolismo , Diferenciação Celular , Síndromes de Imunodeficiência/etiologia , Síndromes de Imunodeficiência/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Encurtamento do Telômero , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Senescência Celular/genética , Senescência Celular/imunologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Citocinas/metabolismo , Humanos , Imunofenotipagem , Contagem de Linfócitos , Sirolimo/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacos