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- Title
IFN-γ production in human NK cells through the engagement of CD8 by soluble or surface HLA class I molecules.
- Authors
Spaggiari, Grazia Maria; Contini, Paola; Negrini, Simone; Dondero, Alessandra; Carosio, Roberta; Ghio, Massimo; Puppo, Francesco; Indiveri, Francesco; Zocchi, Maria Raffaella; Poggi, Alessandro
- Abstract
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.
- Publication
European Journal of Immunology, 2003, Vol 33, Issue 11, p3049
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200323981