The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo
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The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo. / Duncan, G S; Mittrücker, H W; Kägi, D; Matsuyama, T; Mak, T W.
In: J EXP MED, Vol. 184, No. 5, 01.11.1996, p. 2043-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo
AU - Duncan, G S
AU - Mittrücker, H W
AU - Kägi, D
AU - Matsuyama, T
AU - Mak, T W
PY - 1996/11/1
Y1 - 1996/11/1
N2 - The activation of natural killer (NK) cells, cytotoxic lymphocytes capable of major histocompatibility complex (MHC)-unrestricted killing and early antiviral defense, is temporally related to the increased interferon (IFN)-alpha/beta production that is seen in the viral infection of mice. Type I IFN (IFN-alpha/beta) are expressed in many cell types early after primary viral infection and have been shown to mediate resistance against a variety of viruses. In this study, the role of the transcriptional activator IFN regulatory factor-1 (IRF-1) in murine NK cell activity was assessed. IRF-1-deficient mice displayed a normal frequency of NK marker-positive cells, but exhibited greatly reduced NK cell-mediated cytotoxicity after both virus infection and stimulation with the IFN inducer polyinosinic:polycytidilic acid in vivo. In vitro, cytolytic activity in IRF-1-deficient NK cells remained defective after stimulation with IFN-beta, IL-2, and IL-12. IRF-1-deficient mice were unable to eliminate syngeneic MHC class I-negative tumor cells in vivo, and had a reduced ability to reject parental semi-allogeneic donor cells from the circulation. Thus, IRF-1 is essential for the induction of NK cell-mediated cytotoxicity and for the in vivo effector functions that are mediated by this activity.
AB - The activation of natural killer (NK) cells, cytotoxic lymphocytes capable of major histocompatibility complex (MHC)-unrestricted killing and early antiviral defense, is temporally related to the increased interferon (IFN)-alpha/beta production that is seen in the viral infection of mice. Type I IFN (IFN-alpha/beta) are expressed in many cell types early after primary viral infection and have been shown to mediate resistance against a variety of viruses. In this study, the role of the transcriptional activator IFN regulatory factor-1 (IRF-1) in murine NK cell activity was assessed. IRF-1-deficient mice displayed a normal frequency of NK marker-positive cells, but exhibited greatly reduced NK cell-mediated cytotoxicity after both virus infection and stimulation with the IFN inducer polyinosinic:polycytidilic acid in vivo. In vitro, cytolytic activity in IRF-1-deficient NK cells remained defective after stimulation with IFN-beta, IL-2, and IL-12. IRF-1-deficient mice were unable to eliminate syngeneic MHC class I-negative tumor cells in vivo, and had a reduced ability to reject parental semi-allogeneic donor cells from the circulation. Thus, IRF-1 is essential for the induction of NK cell-mediated cytotoxicity and for the in vivo effector functions that are mediated by this activity.
KW - Animals
KW - Antigens
KW - Antigens, Surface
KW - Cell Transplantation
KW - Cytotoxicity, Immunologic
KW - DNA-Binding Proteins
KW - H-2 Antigens
KW - Interferon Regulatory Factor-1
KW - Interferon-beta
KW - Interleukin-12
KW - Interleukin-2
KW - Killer Cells, Natural
KW - Lectins, C-Type
KW - Lymphocyte Activation
KW - Lymphocytic Choriomeningitis
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - NK Cell Lectin-Like Receptor Subfamily B
KW - Neoplasms, Experimental
KW - Phosphoproteins
KW - Proteins
KW - Transcription Factors
M3 - SCORING: Journal article
C2 - 8920893
VL - 184
SP - 2043
EP - 2048
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 5
ER -