| The role of T cells in the foreign body response to biomaterials has not been elucidated. Clinically, however patients implanted with a left ventricular assist device, a polyurethane, exhibit biomaterial induced T cell activation. Our laboratory has demonstrated that lymphocytes enhance macrophage adhesion and fusion in vitro, although it is not known if these effects are mediated by T cells. The goal of this research was to investigate potential T cell interactions in the foreign body response to three clinically relevant non-biodegradable synthetic biomedical polymers: Elasthane 80A (PEU), silicone rubber (SR), and polyethylene terephthalate (PET). Chapter 2 addresses the role that adaptive immunity, specifically memory, may play by evaluating the primary and secondary host response. We observed quantitative increases in T cells following secondary biomaterial exposure without alterations in T cell subset distributions. In Chapter 3, further characterization of the biomaterial implant site was carried out by analysis of cytokine profiles. The presence of a polymer implant did affect cytokine profiles. Most notably, IL-6 and TNFalpha levels were significantly greater in those animals implanted with PEU and SR, materials that do not promote fusion. In Chapter 4, in vitro T cell activation was investigated using human blood mononuclear cells and assessed by upregulation of cell surface activation markers, proliferation, and IL-2 production. T cell activation was not induced in response to the three biomaterials. Therefore in Chapter 5, biomaterials were implanted in T cell deficient mice to determine whether T cells are required in the foreign body response in vivo. This study showed that there are pathways that do not require thymus-matured T lymphocytes which lead to a normal foreign body response to biomaterials in a murine model. Finally in Chapter 6, the role of IL-4 and IL-13 in foreign body giant cell formation in vivo was evaluated and IL-4 was found to be the main fusion inducing cytokine at the biomaterial implant site. This research further characterized the foreign body response in vivo, demonstrated that T cells are not activated in response to these synthetic biomaterials and the foreign body response can progress normally without thymus-matured T cells. |
