Analysis of the mechanisms involved in NK resistance induced by a new tumor factor NK-RIF.
The mechanisms involved in susceptibility or resistance of neoplasic cells to lysis by NK cells are not well known. We have recently described a 12-kDa factor (NK-RIF), produced and released by different tumor cell lines, making K562 resistant to NK lysis without affecting the cytotoxic function of NK effector cells. In this paper we further study the mechanism involved in NK resistance of K562 mediated by NK-RIF and its biological implications. The results show that NK-RIF does not affect the binding capacity of target and effector cells nor the levels of HLA class I antigen expression on the target cells, as a proof that resistance to NK-mediated lysis is not always associated with a defect in target effector binding or with an increased MHC class I antigen expression. However NK-RIF-treated K562 loses its capacity to induce NK cell activation and the subsequent capacity to release NKCF and makes K562 resistant to lysis by NKCF. Therefore our results show that induction of resistance to NK cytotoxicity can be the result of the modulation of target structures responsible for inducing effector cell activation without affecting target/effector binding molecules. This indicates that the structures involved in adherence and activation of NK cells have a different nature and that molecules other than HLA participate in NK resistance.
Department of Biochemistry and Immunology, Faculty of Medicine, Reina Sofia Hospital, University of Córdoba, Spain.
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Solana
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Alonso
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Ramirez
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Carracedo
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Serrano
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Yiangou
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Peña
D001685:Biological Factors / Q000502:physiology*; D002460:Cell Line; D016207:Cytokines; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D013491:Suppressor Factors, Immunologic / Q000502:physiology*
D001685:Biological Factors; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic