Int J Biol Sci 2009; 5(2):182-191. doi:10.7150/ijbs.5.182 This issue

Research Paper

Association between Apoptotis and CD4+/CD8+ T-Lymphocyte Ratio in Aseptic Loosening after Total Hip Replacement

Stefan Landgraeber1✉, Marius von Knoch1, Franz Löer1, Jochen Brankamp1, Michael Tsokos2, Florian Grabellus3, Kurt Werner Schmid3, Martin Totsch3

1. Department of Orthopaedics, University of Duisburg-Essen, Pattbergstrasse 1-3, 45239 Essen, Germany
2. Department of Forensic Pathology, Institute of Legal Medicine, Charité Universitätsmedizin Berlin, Turmstrasse 21, 10559 Berlin, Germany
3. Institute of Pathology and Neuropathpology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany

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Landgraeber S, von Knoch M, Löer F, Brankamp J, Tsokos M, Grabellus F, Schmid KW, Totsch M. Association between Apoptotis and CD4+/CD8+ T-Lymphocyte Ratio in Aseptic Loosening after Total Hip Replacement. Int J Biol Sci 2009; 5(2):182-191. doi:10.7150/ijbs.5.182. Available from

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Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. While the osteolytic cascade initiated by cytokine release from macrophages has been studied extensively, the involvement of T-lymphocytes in this context is controversial and has been addressed by only a few authors. In a former study we detected that the quantity of T-lymphocytes may be influenced by apoptosis in patients with aseptic loosening. In this study we intended to find out more details about the apoptosis-induced shifting of the T-cell number. We focused our interest on the CD4+ and CD8+ T-cells and their relative ratio. Caspase-3 cleaved was evaluated immunohistochemically to detect apoptotic T-cells in capsules and interface membranes from patients with aseptic hip implant loosening and a varying degree of caspase-3 cleaved expression in CD4+ and CD8+ T-lymphocytes was detected. Moreover, a relationship between the intensity of the apoptotic reactions and the radiological extent of osteolysis was observed. The number of CD4+ cells was decreased in the presence of strong apoptotic reactions, respectively extensive osteolysis, while CD8+ cells were affected to a much lower degree. Thus, the CD4+/CD8+ ratio changed from 1.0 in cases with only small areas of periprosthetic osteolysis and minimally intense apoptosis to 0.33 in cases with large areas of osteolysis. This may suggest a causal relationship between the apoptosis-induced shift in the CD4+/CD8+ ratio and the osteolysis respectively aseptic loosening. It is possible that these findings may lead to a new understanding of particle-induced osteolysis.

Keywords: Wear Debris, Osteolysis, Apoptosis, T-Lymphocytes, Immunohistochemistry