CD56dim CD57- NKG2C+ NK cells retaining proliferative potential are possible precursors of CD57+ NKG2C+ memory-like NK cells.,Journal of Leukocyte Biology

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CD56dim CD57- NKG2C+ NK cells retaining proliferative potential are possible precursors of CD57+ NKG2C+ memory-like NK cells.
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-09-15 , DOI: 10.1002/jlb.1ma0720-654rr
Polina A Kobyzeva ₁ , Maria A Streltsova ₁ , Sofya A Erokhina ₁ , Leonid M Kanevskiy ₁ , William G Telford ₂ , Alexander M Sapozhnikov ₁ , Elena I Kovalenko ₁

Affiliation

Formation of the adaptive‐like NK cell subset in response to HCMV infection is associated with epigenetic rearrangements, accompanied by multiple changes in the protein expression. This includes a decrease in the expression level of the adapter chain FcεRIγ, NKp30, and NKG2A receptors and an increase in the expression of NKG2C receptor, some KIR family receptors, and co‐stimulating molecule CD2. Besides, adaptive‐like NK cells are characterized by surface expression of CD57, a marker of highly differentiated cells. Here, it is shown that CD57‐negative CD56^dimNKG2C⁺ NK cells may undergo the same changes, as established by the similarity of the phenotypic expression pattern with that of the adaptive‐like CD57⁺NKG2C⁺ NK cells. Regardless of their differentiation stage, NKG2C‐positive NK cells had increased HLA‐DR expression indicating an activated state, both ex vivo and after cultivation in stimulating conditions. Additionally, CD57⁻NKG2C⁺ NK cells exhibited better proliferative activity compared to CD57⁺NKG2C⁺ and NKG2C⁻ NK cells, while retaining high level of natural cytotoxicity. Thus, CD57⁻NKG2C⁺ NK cells may represent a less differentiated, but readily expanding stage of the adaptive‐like CD57⁺NKG2C⁺ NK cells. Moreover, it is shown that NK cells have certain phenotypic plasticity and may both lose NKG2C expression and acquire it de novo during proliferation, induced by IL‐2 and K562‐mbIL21 feeder cells.

中文翻译：

CD56dim CD57- NKG2C+ NK 细胞保留增殖潜力是 CD57+ NKG2C+ 记忆样 NK 细胞的可能前体。

响应 HCMV 感染的适应性样 NK 细胞亚群的形成与表观遗传重排有关，并伴有蛋白质表达的多种变化。这包括衔接链 FcεRIγ、NKp30 和 NKG2A 受体的表达水平降低，以及 NKG2C 受体、一些 KIR 家族受体和共刺激分子 CD2 的表达增加。此外，适应性样 NK 细胞的特点是表面表达 CD57，这是一种高度分化细胞的标志物。在这里，表明 CD57 阴性 CD56 ^dim NKG2C ⁺ NK 细胞可能经历相同的变化，这由表型表达模式与适应性样 CD57 ⁺ NKG2C ^{+的相似性所证实。}NK细胞。无论其分化阶段如何，NKG2C 阳性 NK 细胞的 HLA-DR 表达增加，表明其处于激活状态，无论是离体还是在刺激条件下培养后。此外，与 CD57 ⁺ NKG2C ⁺和 NKG2C ^{- NK 细胞相比，CD57}^- NKG2C ⁺ NK 细胞表现出更好的增殖活性，同时保持高水平的天然细胞毒性。因此，CD57 ^- NKG2C ⁺ NK 细胞可能代表适应性样 CD57 ⁺ NKG2C ^{+的一个分化程度较低但易于扩展的阶段}NK细胞。此外，研究表明 NK 细胞具有一定的表型可塑性，在 IL-2 和 K562-mbIL21 饲养细胞诱导的增殖过程中，NKG2C 表达可能会丢失并从头获得。

更新日期：2020-09-30

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