IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor

Citation
Y. Hyodo et al., IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor, J IMMUNOL, 162(3), 1999, pp. 1662-1668
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
0022-1767 → ACNP
Volume
162
Issue
3
Year of publication
1999
Pages
1662 - 1668
Database
ISI
SICI code
0022-1767(19990201)162:3<1662:IUPNAW>2.0.ZU;2-S
Abstract
IL-18 is a powerful inducer of IFN-gamma production, particularly in collab oration with IL-12, IL-18, like IL-12, also augments NK activity. Here we i nvestigated the molecular mechanism underlying the up-regulation of killing activity of NK cells by IL-18, IL-18, like IL-12, dose dependently enhance d NK activity of splenocytes. This action was further enhanced by costimula tion with IL-12. Treatment with anti-IL-2R Ab did not affect IL-18- and/or IL-12-augmented NK activity, and splenocytes from IFN-gamma-deficient mice showed enhanced NK activity. following stimulation with IL-12 and/or IL-18. Splenocytes from the mice deficient in both IL-12 and IL-18 normally respo nded to IL-18 and/or IL-12 with facilitated NK activity, suggesting that fu nctional NK cells develop in the absence of IL-12 and IL-18. IL-18R, as wel l as IL-12R mRNA, was constitutively expressed in splenocytes from SCID mic e, which lack T cells and B cells but have intact NK cells, and in those fr om IL-12 and IL-18 double knockout mice. NK cells isolated from SCID spleno cytes expressed IL-18R on their surface. IL-18, in contrast to IL-12, did n ot enhance mRNA expression of perforin, a key molecule for exocytosis-media ted cytotoxicity. However, pretreatment with concanamycin A completely inhi bited this IL-18- and/or IL-12-augmented NK activity. Furthermore, IL-18, l ike IL-12, failed to enhance NK activity of splenocytes from perforin-defic ient mice. These data suggested that NK cells develop and express IL-12R an d IL-18R in the absence of IL-12 or IL-18, and that both IL-18 and IL-12 di rectly and independently augment perforin-mediated cytotoxic activity of NK cells.