IFN-γ production in human NK cells through the engagement of CD8 by soluble or surface HLA class I molecules

Grazia Maria Spaggiari, Paola Contini, Simone Negrini, Alessandra Dondero, Roberta Carosio, Massimo Ghio, Francesco Puppo, Francesco Indiveri, Maria Raffaella Zocchi, Alessandro Poggi

Research output: Contribution to journalArticle


The engagement of CD8 on NK cell surface by either surface or soluble HLA class I (sHLA-I) molecules induces synthesis and secretion of IFN-γ. HLA-I-mediated effects were inhibited by the covering of CD8 with specific anti-CD8 monoclonal antibodies, indicating a direct interaction of HLA-I and CD8. That CD8 ligation induces IFN-γ production was further supported by the finding that cross-linking of CD8 led to release of IFN-γ at similar levels to those obtained with HLA-I. The sHLA-I-induced IFN-γ production via CD8 was strongly down-regulated by the engagement of the inhibitory isoforms of either CD94/NKG2 complex by sHLA-I-non-(A,B,C,G) (putative sHLA-E) or CD158b by sHLA-I-Cw3 allele. Ligation of CD8 did not elicit, different from other activating NK cell surface molecules such as CD16 or CD69, triggering of NK cell-mediated cytolysis. Cyclosporin A, but not concanamycin A, an H+-ATPase vacuolar inhibitor which affects perforin and granzyme release, strongly reduced the sHLA-I-mediated CD8-dependent IFN-γ production but did not affect cytolytic activity of NK cells, suggesting that different biochemical pathways are involved. Altogether, these findings indicate that CD8 engagement by sHLA-I activates a cyclosporin A-dependent pathway leading to production and secretion of IFN-γ which may play a role in the regulation of innate immune responses in humans.

Original languageEnglish
Pages (from-to)3049-3059
Number of pages11
JournalEuropean Journal of Immunology
Issue number11
Publication statusPublished - Nov 2003



  • CD8
  • IFN-γ
  • NK cells
  • Soluble HLA

ASJC Scopus subject areas

  • Immunology

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