CD4 and CD8 T cells reduce inflammation and promote bone healing in response to titanium implants.

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.