Influence of metal ions on human lymphocytes and the generation of titanium-specific T-lymphocytes

Background: There is mounting evidence to suggest the involvement of the immune system by means of activation by metal ions released via biocorrosion, in the pathophysiologic mechanisms of aseptic loosening of orthopedic implants. However, the detailed mechanisms of how metal ions become antigenic and are presented to T-lymphocytes, in addition to how the local inflammatory response is driven, remain to be investigated. Methods: Human T-lymphocytes were cultured in the presence of a variety of metal ions before investigating functional and phenotypic changes using flow cytometric analysis. Additionally, human monocyte-derived dendritic cells (mDC) loaded with metal ions were used as antigen-presenting cells and incubated with naive T-lymphocytes with the aim of generating titanium-specific T-lymphocytes. Results: Using an autologous in vitro model, with mDC treated with Titanium (IV), we were able to induce Titanium (IV)-specific T-lymphocytes. These T-lymphocytes responded in a dose-related manner to Titanium (IV), while they did not cross-react with Titanium (III) or other metal ions, indicating that the new antigenic peptide complexes formed by Titanium (IV) are highly specific. Conclusion: This study showed that mDC exposed to Titanium (IV) are able to induce the generation of Titanium (IV)-specific T-lymphocytes, demonstrating the strong and specific antigenicity of Titanium (IV) ions released by biocorrosion.