Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers.
We previously reported that natural killer cell stimulatory factor (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon gamma (IFN-gamma) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin 2 in this activity. In this study, we show that human NKSF induces IFN-gamma production from both resting and activated human PBL and from freshly isolated murine splenocytes. Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR+ (HLA-DR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-gamma production results in accumulation of IFN-gamma mRNA, is insensitive to cyclosporin A, and synergizes with those mediated by phytohemagglutinin, phorbol diesters, anti-CD3 antibodies, and allogeneic antigens, but not by Ca2+ ionophores. The ability of NKSF to directly induce IFN-gamma production and to synergize with other physiological IFN-gamma inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent.
Chan
S H
SH
Wistar Institute, Philadelphia, Pennsylvania 19104.
Perussia
B
B
Gupta
J W
JW
Kobayashi
M
M
Pospísil
M
M
Young
H A
HA
Wolf
S F
SF
Young
D
D
Clark
S C
SC
Trinchieri
G
G
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015152:Blotting, Northern; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000378:metabolism*
D003524:Cyclosporins; D016207:Cytokines; D006684:HLA-DR Antigens; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma