The Pathogenic Role of Expanded CD8⁺CD28<sup>null</sup> Angiogenic T Cells in ANCA-Associated Vasculitis

<b>Objectives:</b> Angiogenic T cells (Tang) are crucial in promoting angiogenesis, with the loss of CD28 serving as a marker for highly differentiated and senescent T cells. This study aims to investigate the characteristics and potential roles of CD8<sup>+</sup>CD28<sup&...

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Main Authors: Haomiao Shen, Jinlin Miao, Haoyang Sun, Kui Zhang, Renli Liu, Zichao Li, Leyang Zhang, Peiyan Zhang, Jiawei Wang, Bei Zhang, Longyu Chen, Zhaohui Zheng, Ping Zhu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/26
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Summary:<b>Objectives:</b> Angiogenic T cells (Tang) are crucial in promoting angiogenesis, with the loss of CD28 serving as a marker for highly differentiated and senescent T cells. This study aims to investigate the characteristics and potential roles of CD8<sup>+</sup>CD28<sup>null</sup> Tang in patients with ANCA-associated vasculitis (AAV). <b>Methods:</b> A cohort of AAV patients and matched healthy controls (HCs) were analyzed. Flow cytometry was used to assess the profiles of circulating CD8<sup>+</sup>CD28<sup>null</sup> Tang. In vitro functional assays were performed to evaluate the pathogenic properties of CD8<sup>+</sup>CD28<sup>null</sup> Tang. <b>Results</b>: CD8<sup>+</sup>CD28<sup>null</sup> Tang levels were significantly higher in the peripheral blood of AAV patients compared to HCs, and their levels were further increased in AAV patients with MPO⁺, p-ANCA⁺, or interstitial lung disease compared to their respective control groups. Additionally, there was a positive correlation between both the percentage and absolute count of CD8<sup>+</sup>CD28<sup>null</sup> Tang and the Birmingham Vasculitis Activity Score (BVAS). In patients with a good treatment response, both the percentage and absolute count of CD8<sup>+</sup>CD28<sup>null</sup> Tang were significantly reduced, and this reduction was positively correlated with the decrease in BVAS scores. In vitro studies revealed that CD8<sup>+</sup>CD28<sup>null</sup> Tang displayed enhanced chemotactic properties, induced apoptosis in human umbilical vein endothelial cells (HUVECs), and inhibited their proliferation, migration, and tube formation. <b>Conclusions:</b> AAV patients exhibit increased levels of circulating CD8<sup>+</sup>CD28<sup>null</sup> Tang, which can be reduced following effective treatment. Furthermore, CD8<sup>+</sup>CD28<sup>null</sup> Tang may contribute to the pathogenesis of AAV by promoting apoptosis and inhibiting the proliferation, migration, and tube formation of HUVECs.
ISSN:2227-9059