TY - JOUR
T1 - Inefficient protection of human TAP-deficient fibroblasts from autologous NK cell-mediated lysis by cytokines inducing HLA class I expression
AU - Zimmer, Jacques
AU - Donato, Lionel
AU - Hanau, Daniel
AU - Cazenave, Jean Pierre
AU - Moretta, Alessandro
AU - Tongio, Marie Marthe
AU - De La Salle, Henri
PY - 1999
Y1 - 1999
N2 - 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-α, IFN-γ, TNF-α and IFN-γ + TNF-α) 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-α, IFN-γ or IFN-γ + TNF-α, 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.
AB - 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-α, IFN-γ, TNF-α and IFN-γ + TNF-α) 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-α, IFN-γ or IFN-γ + TNF-α, 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.
KW - Cytokine
KW - Fibroblast
KW - HLA class I
KW - NK cell
KW - TAP deficiency
UR - http://www.scopus.com/inward/record.url?scp=0032910215&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1521-4141(199904)29:04<1286::AID-IMMU1286>3.0.CO;2-L
DO - 10.1002/(SICI)1521-4141(199904)29:04<1286::AID-IMMU1286>3.0.CO;2-L
M3 - Article
C2 - 10229096
AN - SCOPUS:0032910215
SN - 0014-2980
VL - 29
SP - 1286
EP - 1291
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -