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C反应蛋白诱导的T细胞活化是一种间接的单核细胞依赖机制,涉及CD80/CD28途径。

C-reactive protein induced T cell activation is an indirect monocyte-dependent mechanism involving the CD80/CD28 pathway.

作者信息

Thomé Julia, Limmer Julia, Brose Teresa Z, Zeller Johannes, Chevalier Nina, Schäfer Anna-Lena, Schneider Laura, Lind Maike, Christmann Thierry, Dreck Marie, Kreuzaler Sheena, Braig David, Peter Karlheinz, Pankratz Franziska, Eisenhardt Steffen U

机构信息

Department of Plastic and Hand Surgery, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Department of Dermatology, Medical Center - University of Freiburg, Freiburg, Germany.

出版信息

Front Immunol. 2025 Jul 18;16:1622865. doi: 10.3389/fimmu.2025.1622865. eCollection 2025.

DOI:10.3389/fimmu.2025.1622865
PMID:40755767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12313514/
Abstract

INTRODUCTION

T cells are major components of the immune system. Their activation requires interaction between the T cell receptor and co-stimulatory molecules, crucial during infection, inflammation, and allogeneic rejection. Monomeric CRP (mCRP) is a known modulator of inflammation and particularly the innate immune response, however its interaction with T cells as part of the adaptive immune response remains unclear.

METHODS

Peripheral blood mononuclear cells (PBMC) and T cells were isolated. Flow cytometric analysis was conducted to evaluate Fcγ receptor CD16 expression on T cells, the binding of CRP to T cells, and its impact on proliferation and apoptosis. T cell activation was assessed after 1, 2, 3, 5 and 7 days by assessing CD69 and CD25 expression, and under various conditions including coculture with monocytes and several inhibitory factors.

RESULTS

T cells express CD16 that binds mCRP in a concentration-dependent manner, and particularly on activated T cells. While mCRP reduces apoptosis and accelerates proliferation in T cells, it does not independently activate them. However, activation of monocytes by mCRP leads to T cell activation, indicating a direct cell to cell interaction during CRP-induced activation. This effect could be alleviated by inhibition of the CD80/CD28 pathway.

CONCLUSION

CRP does not activate T Cells directly but via PI3-kinase-dependent activation of monocytes and subsequent CD80/CD28 cell to cell contact. The findings suggest the effects of CRP on T cells depend on their environment and the presence of other proinflammatory agents.

摘要

引言

T细胞是免疫系统的主要组成部分。它们的激活需要T细胞受体与共刺激分子之间的相互作用,这在感染、炎症和同种异体排斥反应中至关重要。单体CRP(mCRP)是一种已知的炎症调节剂,尤其是先天性免疫反应的调节剂,然而,其作为适应性免疫反应一部分与T细胞的相互作用仍不清楚。

方法

分离外周血单核细胞(PBMC)和T细胞。进行流式细胞术分析以评估T细胞上Fcγ受体CD16的表达、CRP与T细胞的结合及其对增殖和凋亡的影响。在1、2、3、5和7天后,通过评估CD69和CD25的表达,并在包括与单核细胞共培养和几种抑制因子在内的各种条件下,评估T细胞的激活情况。

结果

T细胞表达CD16,其以浓度依赖性方式结合mCRP,特别是在活化的T细胞上。虽然mCRP减少T细胞凋亡并加速其增殖,但它不能独立激活它们。然而,mCRP激活单核细胞会导致T细胞激活,表明在CRP诱导的激活过程中存在直接的细胞间相互作用。这种作用可通过抑制CD80/CD28途径来缓解。

结论

CRP不是直接激活T细胞,而是通过PI3激酶依赖性激活单核细胞以及随后的CD80/CD28细胞间接触来激活。这些发现表明CRP对T细胞的影响取决于它们的环境和其他促炎因子的存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/de975b8518f8/fimmu-16-1622865-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/089cd94699be/fimmu-16-1622865-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/9e5385175af4/fimmu-16-1622865-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/e6f1ae05037d/fimmu-16-1622865-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/244d10cffa46/fimmu-16-1622865-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/de975b8518f8/fimmu-16-1622865-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/089cd94699be/fimmu-16-1622865-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/9e5385175af4/fimmu-16-1622865-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/e6f1ae05037d/fimmu-16-1622865-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/244d10cffa46/fimmu-16-1622865-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b5/12313514/de975b8518f8/fimmu-16-1622865-g005.jpg

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