The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo

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 -