CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome
CD57 identifies T cells with functional senescence before terminal differentiation and relative telomere shortening in patients with activated PI3 kinase delta syndrome
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DOI：
10.1111/imcb.12169
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发表时间：
2018-11-01
影响因子：
4
通讯作者：
Rensing-Ehl, Anne
中科院分区：
文献类型：
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作者：
Daball, Paola Cura;Ferreira, Monica Sofia Ventura;Rensing-Ehl, Anne
伴有CD 57（+）CD 8（+）T细胞蓄积的过早T细胞免疫衰老与原发性免疫缺陷（包括活化PI 3激酶δ综合征（APDS））中的免疫缺陷和自身免疫有关。为了解决CD 57是否标志着在成人个体中观察到的典型衰老T细胞群体或识别APDS中的独特群体，我们比较了大多数儿科APDS患者的CD 57（+）CD 8（+）T细胞与具有类似显著衰老T细胞的健康成人的T细胞。来自APDS患者的CD 57（+）CD 8（+）T细胞分化程度较低，具有更多的CD 27（+）CD 28（+）效应记忆T细胞，显示PD 1和Eomesodermin表达增加。此外，幼稚T细胞向CD 57（+）CD 8（+）T细胞的转变与特征性端粒缩短无关。然而，它们显示出增加的干扰素-γ分泌，增强的脱粒和减少的体外增殖典型的衰老的CD 57（+）CD 8（+）T细胞。因此，过度活跃的PI 3激酶信号传导有利于CD 57（+）CD 8（+）T细胞群体的过早积累，其显示出典型衰老T细胞的大多数功能特征，但在分化和相对端粒缩短方面不同。初步观察表明，这种特定的分化状态可能提供了机会，以恢复过早的T细胞免疫衰老及其潜在的贡献，炎症和免疫缺陷的APDS。
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 naive 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.