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Queen Mary University of LondonQueen Mary University of London
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School of Engineering and Materials Science
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PhD Thesis: Modelling T lymphocyte reactions to biomedical materials

Author: HERCUS, Beth Justine

Year: 2005

Supervisor(s): Pankaj Vadgama

Aseptic loosening (AL) is a major complication of total joint replacement. This thesis aims to ascertain whether T cells are involved in the inflammation which occurs in response to implant derived wear debris. It further aims to identify whether allergy to nickel might influence the immune response occurring in AL. Analysis of tissue removed at the time of revision surgery was carried out using immunohistochemistry, polymerase chain reaction (PCR) and western blotting (WB). A guinea-pig model was used for intraosseous implantation studies of solid stainless steel rods or cobalt chrome alloy (CoCr) particles suspended in agar. Histochemical and immunohistochemical analysis of joints are soft tissues (Spleen and liver) retrieved at post-mortem was performed. T cells represented on average 10%-12% of the total cellular population of the interface. CD4+T cells predominated as compared to CD8+ T cell at a ratio of 5 to 1. PCR detection of T cell cytokine expression was predominated by interleukin (IL)-2 (87%) followed by IL-13and IFNγ (67%), IL-4 and IL-10 (60%), IL-12 (47%) and least of all IL-5 (33%). Western blotting detected IL-17 in 88% of cases tested, fractalkine in 77% and CD40 in 74% of cases tested. Sensitisation to nickel was successful in guinea pigs and when compared to non-sensitised animals in response to alloy implantation showed an increase in cellular responses both at the implant site and in the spleen. Responses to particulate CoCr was greater than that to SS rods regardless of sensitisation status, and responses to both implant materials was greater as compared to control animals.

This thesis contributes to the expanding picture of the role of T lymphocyte in periprosthetic inflammation and osteolysis that is currently unfolding.