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.
Department of Histology and Embryology, Warsaw Medical School, Poland.
J
J
Malejczyk
D000818:Animals; D002358:Cartilage, Articular / Q000276:immunology*; D002469:Cell Separation; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007370:Interferon Type I / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains
D007370:Interferon Type I; D007376:Interleukin-2