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中性粒细胞- T 细胞接触的结果取决于两种细胞类型的激活状态。

The Outcome of Neutrophil-T Cell Contact Differs Depending on Activation Status of Both Cell Types.

机构信息

Centre for Inflammation Research, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, United Kingdom.

出版信息

Front Immunol. 2021 Mar 30;12:633486. doi: 10.3389/fimmu.2021.633486. eCollection 2021.

Abstract

Neutrophils and T cells exist in close proximity in lymph nodes and inflamed tissues during health and disease. They are able to form stable interactions, with profound effects on the phenotype and function of the T cells. However, the outcome of these effects are frequently contradictory; in some systems neutrophils suppress T cell proliferation, in others they are activatory or present antigen directly. Published protocols modelling these interactions do not reflect the full range of interactions found ; they do not examine how activated and naïve T cells differentially respond to neutrophils, or whether de-granulating or resting neutrophils induce different outcomes. Here, we established a culture protocol to ask these questions with human T cells and autologous neutrophils. We find that resting neutrophils suppress T cell proliferation, activation and cytokine production but that de-granulating neutrophils do not, and neutrophil-released intracellular contents enhance proliferation. Strikingly, we also demonstrate that T cells early in the activation process are susceptible to suppression by neutrophils, while later-stage T cells are not, and naïve T cells do not respond at all. Our protocol therefore allows nuanced analysis of the outcome of interaction of these cells and may explain the contradictory results observed previously.

摘要

中性粒细胞和 T 细胞在健康和疾病状态下存在于淋巴结和炎症组织中。它们能够形成稳定的相互作用,对 T 细胞的表型和功能产生深远影响。然而,这些影响的结果往往相互矛盾;在一些系统中,中性粒细胞抑制 T 细胞增殖,而在另一些系统中,它们具有激活作用或直接呈递抗原。已发表的模拟这些相互作用的方案并没有反映出实际存在的全部相互作用;它们没有研究激活和幼稚 T 细胞对中性粒细胞的反应有何不同,也没有研究脱颗粒或静止的中性粒细胞是否会产生不同的结果。在这里,我们建立了一种培养方案,用于用人 T 细胞和自体中性粒细胞来回答这些问题。我们发现静止的中性粒细胞会抑制 T 细胞的增殖、活化和细胞因子的产生,但脱颗粒的中性粒细胞不会,中性粒细胞释放的细胞内物质会增强增殖。引人注目的是,我们还证明,在激活过程早期的 T 细胞易受中性粒细胞的抑制,而晚期 T 细胞则不受影响,幼稚 T 细胞根本没有反应。因此,我们的方案可以对这些细胞相互作用的结果进行细致的分析,并可能解释以前观察到的相互矛盾的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa01/8042376/701c79c925d4/fimmu-12-633486-g001.jpg

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