T cell subset distributions following primary and secondary implantation at subcutaneous biomaterial implant sites

Abstract

Synthetic biomaterials are considered to be nonimmunogenic. Therefore, the role that adaptive immunity may play in the host response to implanted synthetic biomaterials has not been extensively studied. Cardinal features of adaptive immunity include specificity and T cell responses, which are greater and more effective with upregulation of activation receptors upon rechallenge. We compared the primary and secondary in vivo host response to three synthetic biomaterials: Elasthane 80A, silicone rubber, and polyethylene terephthalate using a cage implant model in Sprague Dawley rats. The synthetic biomedical polymers were subcutaneously implanted in cages for 14 days. Following explantation of the cages and a 2 week healing period, rats were implanted with cages containing the biomedical polymers for an additional 2 weeks. The cellular exudates within the cages were analyzed 4, 7, and 14 days post primary and secondary implantation by flow cytometry for the following cell types: T cells (inclusive of CD8(+), CD4(+), and CD4(+)/CD25(+) subsets), B cells, granulocytes, and macrophages. At day 14 following secondary implantation, there was an increase in T cells, granulocytes, and macrophages in the exudates when compared with primary implantation for all groups inclusive of the empty cage control. However, CD4(+)/CD8(+) ratios, the percentage of CD4(+)CD25(+) T cells, and the macrophage surface adhesion/fusion did not vary significantly upon secondary implantation. Despite a quantitative increase in T cells following secondary biomaterial exposure, T cell subset distribution did not change, indicating nonspecific recruitment rather than an adaptive immune response.

Serum profile of pro- and anti-inflammatory cytokines in rats following implantation of low-temperature plasma-modified titanium plates

“…Macrophages and other phagocytic cells were found to play a major role within these reactions [4] while T cells are also involved [5]. However, more studies are needed to elucidate their exact role [6,7].…”

In vivo investigation of the inflammatory response against allylamine plasma polymer coated titanium implants in a rat model

“…In the context of this response, macrophages and other phagocytic cells play a central role [10]. Furthermore, T-cells have been implicated in the host reaction after implantation of biomaterials [11], although their exact role remains unknown [12,13]. In the context of the present implant improvement approach, study of inflammatory response is of special importance, since the coated titanium surface will be the cell contacting material.…”

Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells

“…These interactions are also dependent on biomaterial surface chemistry (MacEwan et al, 2005) and lead to biomaterial-dependent cytokine production (Chang et al, 2008a) and both direct and indirect interactions with lymphocytes enhance macrophage/FBGC biomaterial-dependent activation for cytokine production (Chang et al, 2008b; Chang et al, 2009). In vivo in the context of the foreign body reaction, we have demonstrated that secondary responses to biomaterial implantation are characterized by recruitment of both T lymphocytes and phagocytic cells (Rodriguez et al, 2008). …”