CD 57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI 3 kinase delta syndrome

Premature T‐cell immunosenescence with CD 57 + CD 8 + T‐cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI 3 kinase delta syndrome ( APDS ). To address whether CD 57 marks the typical senescent T‐cell population seen in adult individuals or identifies a distinct population in APDS , we compared CD 57 + CD 8 + T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD 57 + CD 8 + T cells from APDS patients were less differentiated with more CD 27 + CD 28 + effector memory T cells showing increased PD 1 and Eomesodermin expression. In addition, transition of naïve to CD 57 + CD 8 + 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 CD 57 + CD 8 + T cells. Thus, hyperactive PI 3 kinase signaling favors premature accumulation of a CD 57 + CD 8 + 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 .