Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, 70 S. Madison Street, Room 3328, Richmond, VA 23220, United States.
Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, 70 S. Madison Street, Room 3328, Richmond, VA 23220, United States.
Acta Biomater. 2024 Apr 15;179:385-397. doi: 10.1016/j.actbio.2024.03.022. Epub 2024 Mar 29.
T cells are adaptive immune cells essential in pathogenic response, cancer, and autoimmune disorders. During the integration of biomaterials with host tissue, T cells modify the local inflammatory environment by releasing cytokines that promote inflammatory resolution following implantation. T cells are vital for the modulation of innate immune cells, recruitment and proliferation of mesenchymal stem cells (MSCs), and formation of functional tissue around the biomaterial implant. We have demonstrated that deficiency of αβ T cells promotes macrophage polarization towards a pro-inflammatory phenotype and attenuates MSC recruitment and proliferation in vitro and in vivo. The goal of this study was to understand how CD4 and CD8 T cells, subsets of the αβ T cell family, impact the inflammatory response to titanium (Ti) biomaterials. Deficiency of either CD4 or CD8 T cells increased the proportion of pro-inflammatory macrophages, lowered anti-inflammatory macrophages, and diminished MSC recruitment in vitro and in vivo. In addition, new bone formation at the implantation site was significantly reduced in T cell-deficient mice compared to T cell-competent mice. Deficiency of CD4 T cells exacerbated these effects compared to CD8 T cell deficiency. Our results show the importance of CD4 and CD8 T cells in modulating the inflammatory response and promoting new bone formation in response to modified Ti implants. STATEMENT OF SIGNIFICANCE: CD4 and CD8 T cells are essential in modulating the peri-implant microenvironment during the inflammatory response to biomaterial implantation. This study shows that deficiency of either CD4 or CD8 T cell subsets altered macrophage polarization and reduced MSC recruitment and proliferation at the implantation site.
T 细胞是适应性免疫细胞，在病原体反应、癌症和自身免疫性疾病中至关重要。在生物材料与宿主组织整合的过程中，T 细胞通过释放细胞因子来改变局部炎症环境，促进植入后的炎症消退。T 细胞对于调节先天免疫细胞、间充质干细胞（MSCs）的募集和增殖以及生物材料植入周围功能性组织的形成至关重要。我们已经证明，αβ T 细胞的缺乏会促进巨噬细胞向促炎表型极化，并减弱 MSC 在体外和体内的募集和增殖。本研究的目的是了解 CD4 和 CD8 T 细胞（αβ T 细胞家族的亚群）如何影响对钛（Ti）生物材料的炎症反应。CD4 或 CD8 T 细胞的缺乏增加了促炎巨噬细胞的比例，降低了抗炎巨噬细胞的比例，并减少了体外和体内的 MSC 募集。此外，与 T 细胞功能正常的小鼠相比，T 细胞缺乏小鼠在植入部位的新骨形成明显减少。与 CD8 T 细胞缺乏相比，CD4 T 细胞的缺乏加剧了这些影响。我们的结果表明，CD4 和 CD8 T 细胞在调节炎症反应和促进对改性 Ti 植入物的新骨形成方面具有重要作用。
