Inefficient protection of human TAP-deficient fibroblasts from autologous NK cell-mediated lysis by cytokines inducing HLA class I expression.
We studied HLA class I expression and susceptibility to lysis of activated autologous NK cells in normal and TAP-deficient fibroblasts. These cells were cultured in the presence or absence of cytokines known to increase the surface expression of HLA class I molecules. All the cytokines tested (IFN-alpha, IFN-gamma, TNF-alpha and IFN-gamma + TNF-alpha) increased the expression of HLA class I molecules on fibroblasts after 48-h culture, but on TAP-deficient cells this expression remained very low as compared to that of normal cells. In the presence of IFN-alpha, IFN-gamma or IFN-gamma + TNF-alpha, normal target cells became resistant to lysis by autologous NK cells, whereas this effect was much less pronounced in the case of TAP-deficient fibroblasts. Addition of an anti-HLA class I mAb to fibroblasts treated with cytokines increased lysis of normal but not of TAP-deficient cells. These results suggest that activated TAP-deficient NK cells are strongly cytotoxic to normal autologous cells and that these cells cannot be efficiently protected by cytokines inducing HLA class I expression. Thus, in human TAP deficiency, activated NK cells may contribute to the progressive lung degradation which characterizes the clinical course of these patients.
Zimmer
J
J
CJF INSERM 94-03, Etablissement de Transfusion Sanguine, Strasbourg, France.
Donato
L
L
Hanau
D
D
Cazenave
J P
JP
Moretta
A
A
Tongio
M M
MM
de la Salle
H
H
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D014409:Tumor Necrosis Factor-alpha; C071692:TAP2 protein, human; D007372:Interferons