Natural anti-chondrocyte cytotoxicity of normal human peripheral blood mononuclear cells

Natural cytotoxic activity of peripheral blood mononuclear cells (PBMC) from healthy humans against normal epiphyseal chondrocytes was assessed in the 51Cr-release assay. PBMC lysed human fetal chondrocytes, while exerting only low activity against xenogeneic rat chondrocytes. Anti-human chondrocyte cytotoxicity was also demonstrated with normal human splenocytes. Peripheral blood anti-chondrocyte effector cells were shown to be plastic nonadherent and nonphagocytic. Cell separation by sheep red blood cells rosette sedimentation has revealed that most of the anti-chondrocyte activity was found in the T cell-depleted fraction. Only a low activity was present in the T cell-enriched fraction. Depletion of cells endowed with receptor for the Fc portion of the IgG molecule by either IgG-coated ox red blood cells rosette sedimentation or treatment with natural killer (NK) cell-specific anti-Leu-11b monoclonal antibody and complement resulted in almost complete elimination of cells responsible for chondrocyte lysis. Short-term (3-hr) preincubation of PBMC with interferon-alpha strongly augmented their anti-chondrocyte cytotoxicity. On the other hand, no stimulation of chondrocyte lysis was seen after a 3-hr preincubation with interleukin 2 although this treatment increased significantly NK cell-mediated lysis of K-562 leukemic cells. Using competitive assay it has been demonstrated that 51Cr-labeled chondrocyte lysis can be inhibited by addition of "cold" human chondrocytes as well as by cold K-562 cells. Only low inhibition of lysis was seen with cold xenogeneic rat chondrocytes. All these results show that natural anti-chondrocyte effectors share phenotypic and functional properties with typical NK cells.