The role of t lymphocytes in the periprosthetic inflammation of patients with total joint implant failure and osteolysis

Total joint replacement is generally a very successful procedure. In a subset of patients, however, implant survival is limited due to a periprosthetic inflammation which is often accompanied by severe osteolysis. To examine the nature of the inflammatory process, we have analyzed the molecular diversity of tissue infiltrating T cells. The majority of T cells in the periprosthetic membrane are CD4+ and are either arranged in lymphocytic aggregates or are diffusely distributed in the tissue. In tissues collected from five patients, T cell specificities were analyzed by T cell receptor (TCR) transcript CDR3 length analysis. Sequence analysis was utilized to confirm the clonal identity of TCR transcripts. Each patient had clonally expanded T cells in the periprosthetic membrane. Identical TCR sequences were found at several independent sites of the inflammatory periprosthetic tissue, but not in the peripheral blood. To examine the functional profile of tissue infiltrating T cells, lymphokine transcripts were semiquantified in tissue extracts. In all tissues, T cell products were identified, indicating recent activation of the T cells. Increased periprosthetic bone loss was correlated with increased in situ production of IFN-y. Macrophage derived cytokines (IL-1 and IL-6) were consistently expressed in the tissue but were not predictive for osteolysis. We conclude that IFN-y producing T cells, which are presumably stimulated by a tissue residing antigen, are a critical component of the inflammatory infiltrate associated with implant failure.