Inefficient protection of human TAP-deficient fibroblasts from autologous NK cell-mediated lysis by cytokines inducing HLA class I expression

Jacques Zimmer, Lionel Donato, Daniel Hanau, Jean Pierre Cazenave, Alessandro Moretta, Marie Marthe Tongio, Henri De La Salle

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1286-1291
Number of pages6
JournalEuropean Journal of Immunology
Volume29
Issue number4
DOIs
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • Cytokine
  • Fibroblast
  • HLA class I
  • NK cell
  • TAP deficiency

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