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白细胞介素-12特征:自然杀伤细胞终末CD56+高表达阶段及效应功能。

The IL-12 signature: NK cell terminal CD56+high stage and effector functions.

作者信息

Loza Matthew J, Perussia Bice

机构信息

Department of Microbiology and Immunology, Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, Philadelphia, PA 19107, USA.

出版信息

J Immunol. 2004 Jan 1;172(1):88-96. doi: 10.4049/jimmunol.172.1.88.

Abstract

We report that human peripheral NK cells expressing high CD56 levels (CD56(+high)) are terminally differentiated cells indistinguishable from mature NK cells recently activated in the presence of IL-12, and not a functionally distinct NK-cell subset or progenitors to mature CD56(+low) NK cells. CD56(+high) NK cells coexpress all differentiation Ags constitutive or inducible in mature (CD56(+)) NK cells, except CD16, present at lower level than on most mature NK cells. Also, activation markers, activating receptors and adhesion molecules, and most inducible receptors are expressed exclusively and constitutively and are inducible at higher levels on CD56(+high) than on CD56(+low) NK cells. Consistent with their activated phenotype, many CD56(+high) NK cells are cycling and mediate heightened effector functions (proliferation, IFN-gamma and IL-10 but not IL-13 production) in response to IL-12 and other NK cell-specific stimuli. Conversely, IL-12 induces on CD56(+low) NK cells all markers constitutively expressed on the CD56(+high) NK cells, concomitantly preventing the IL-2 (and IL-15)-inducible expression of NKp44 and CD16 re-expression after immune complex-induced down-modulation, and CD56(-/+low) NK cells acquire a CD56(+high) NK cell phenotype in short term in vitro culture with IL-12. The significance of these findings to the NK cell-mediated regulation of immune responses and NK cell development is discussed.

摘要

我们报告称,表达高水平CD56(CD56(+high))的人外周自然杀伤(NK)细胞是终末分化细胞,与在白细胞介素-12(IL-12)存在下最近被激活的成熟NK细胞无法区分,并非功能上独特的NK细胞亚群或成熟CD56(+low) NK细胞的祖细胞。CD56(+high) NK细胞共同表达成熟(CD56(+))NK细胞中组成性或可诱导性表达的所有分化抗原,但CD16除外,其表达水平低于大多数成熟NK细胞。此外,激活标志物、激活受体和黏附分子以及大多数可诱导性受体在CD56(+high) NK细胞上仅组成性表达,且诱导表达水平高于CD56(+low) NK细胞。与其激活的表型一致,许多CD56(+high) NK细胞处于增殖周期,并且在受到IL-12和其他NK细胞特异性刺激时介导增强的效应功能(增殖、产生γ干扰素和白细胞介素-10,但不产生白细胞介素-13)。相反,IL-12可在CD56(+low) NK细胞上诱导CD56(+high) NK细胞组成性表达的所有标志物,同时可防止免疫复合物诱导下调后IL-2(和IL-15)诱导的NKp44表达以及CD16重新表达,并且在与IL-12进行短期体外培养后,CD56(-/+low) NK细胞可获得CD56(+high) NK细胞表型。本文讨论了这些发现对NK细胞介导的免疫反应调节和NK细胞发育的意义。

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