Tags

Type your tag names separated by a space and hit enter

Cytokine-induced apoptosis of human natural killer cells identifies a novel mechanism to regulate the innate immune response.
Blood 1997; 89(3):910-8Blood

Abstract

Interferon-gamma (IFN-gamma) is critical for an effective innate immune response against infection. A combination of interleukins (ILs) derived from activated T cells (IL-2) and monocytes (IL-12), or monocytes alone (IL-15 and IL-12), induces optimal production of IFN-gamma from natural killer (NK) cells. The mechanism by which human NK cells downregulate their production of IFN-gamma is unknown. Here we show that the same cytokines that induce human NK cell IFN-gamma production subsequently induce apoptosis of the NK cells. Fas, bcl-2, or bax do not appear to be involved in this process. The mechanism of cytokine-induced apoptosis of human NK cells appears to involve NK cell production of tumor necrosis factor-alpha (TNF-alpha). Neutralization of TNF-alpha or inhibition of TNF-alpha binding to the p80 TNF-alpha receptor partially inhibited apoptosis. Transforming growth factor-beta, which inhibits cytokine-induced NK cell production of IFN-gamma and TNF-alpha, also decreased cytokine-induced NK cell apoptosis. Costimulation of a CD3-CD56+ NK leukemia cell line with IL-2 and IL-12 or IL-15 and IL-12 induced apoptosis in vitro, which increased when combined with a chemotherapeutic agent. In summary, costimulation of human NK cells via the IL-2 receptor and the IL-12 receptor induces significant IFN-gamma production, followed by NK cell apoptosis and a decline in IFN-gamma production. Hence, cytokines that activate this innate immune response may also serve to limit it via apoptosis. This novel observation may have implications for the regulation of the innate immune response during infection, the toxicity of combination cytokine therapy, and the treatment of NK cell leukemia.

Authors+Show Affiliations

Department of Hematologic Oncology and Bone Marrow Transplantation, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9028322

Citation

Ross, M E., and M A. Caligiuri. "Cytokine-induced Apoptosis of Human Natural Killer Cells Identifies a Novel Mechanism to Regulate the Innate Immune Response." Blood, vol. 89, no. 3, 1997, pp. 910-8.
Ross ME, Caligiuri MA. Cytokine-induced apoptosis of human natural killer cells identifies a novel mechanism to regulate the innate immune response. Blood. 1997;89(3):910-8.
Ross, M. E., & Caligiuri, M. A. (1997). Cytokine-induced apoptosis of human natural killer cells identifies a novel mechanism to regulate the innate immune response. Blood, 89(3), pp. 910-8.
Ross ME, Caligiuri MA. Cytokine-induced Apoptosis of Human Natural Killer Cells Identifies a Novel Mechanism to Regulate the Innate Immune Response. Blood. 1997 Feb 1;89(3):910-8. PubMed PMID: 9028322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cytokine-induced apoptosis of human natural killer cells identifies a novel mechanism to regulate the innate immune response. AU - Ross,M E, AU - Caligiuri,M A, PY - 1997/2/1/pubmed PY - 1997/2/1/medline PY - 1997/2/1/entrez SP - 910 EP - 8 JF - Blood JO - Blood VL - 89 IS - 3 N2 - Interferon-gamma (IFN-gamma) is critical for an effective innate immune response against infection. A combination of interleukins (ILs) derived from activated T cells (IL-2) and monocytes (IL-12), or monocytes alone (IL-15 and IL-12), induces optimal production of IFN-gamma from natural killer (NK) cells. The mechanism by which human NK cells downregulate their production of IFN-gamma is unknown. Here we show that the same cytokines that induce human NK cell IFN-gamma production subsequently induce apoptosis of the NK cells. Fas, bcl-2, or bax do not appear to be involved in this process. The mechanism of cytokine-induced apoptosis of human NK cells appears to involve NK cell production of tumor necrosis factor-alpha (TNF-alpha). Neutralization of TNF-alpha or inhibition of TNF-alpha binding to the p80 TNF-alpha receptor partially inhibited apoptosis. Transforming growth factor-beta, which inhibits cytokine-induced NK cell production of IFN-gamma and TNF-alpha, also decreased cytokine-induced NK cell apoptosis. Costimulation of a CD3-CD56+ NK leukemia cell line with IL-2 and IL-12 or IL-15 and IL-12 induced apoptosis in vitro, which increased when combined with a chemotherapeutic agent. In summary, costimulation of human NK cells via the IL-2 receptor and the IL-12 receptor induces significant IFN-gamma production, followed by NK cell apoptosis and a decline in IFN-gamma production. Hence, cytokines that activate this innate immune response may also serve to limit it via apoptosis. This novel observation may have implications for the regulation of the innate immune response during infection, the toxicity of combination cytokine therapy, and the treatment of NK cell leukemia. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9028322/Cytokine_induced_apoptosis_of_human_natural_killer_cells_identifies_a_novel_mechanism_to_regulate_the_innate_immune_response_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=9028322 DB - PRIME DP - Unbound Medicine ER -