Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells.
Fas ligand (FasL), expressed on activated T cells, plays a central role in regulating the immune response by inducing apoptosis in activated lymphocytes through binding to its receptor, Fas. We report here that a newly discovered cytokine, interferon-gamma-inducing factor (IGIF) (H. Okamura et al., Nature 378, 88, 1995), selectively enhances the FasL-mediated cytotoxicity of cloned murine Th1 cells, but not Th0 or Th2 cells. Anti-IFN-gamma antibody (Ab) did not block the IGIF-induced cytotoxicity of Th1 cells, nor did IFN-alpha, IFN-gamma, or TNF-alpha augment the cytotoxic activity of Th1, thus indicating that this enhanced cytotoxicity of Th1 cells was mediated by IGIF. In addition, IL-12 was also found to enhance the FasL-mediated cytotoxicity of Th1 cells, suggesting that Th1 cells possesses receptors for both cytokines although these cytokines can act via different pathways. The results thus show that IGIF, recently proposed as IL-18, might play a potential role in immunoregulation or in inflammation by augmenting the functional activity of FasL on Th1 cells.
Dao
T
T
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., Okayama, Japan.
Ohashi
K
K
Kayano
T
T
Kurimoto
M
M
Okamura
H
H
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D016207:Cytokines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018664:Interleukin-12