Multiple Defects of Immune Cell Function in Mice with Disrupted Interferon-γ Genes
Abstract
Interferon-γ (IFN-γ) is a pleiotrophic cytokine with immunomodulatory effects on a variety of immune cells. Mice with a targeted disruption of the IFN-γ gene were generated. These mice developed normally and were healthy in the absence of pathogens. However, mice deficient in IFN-γ had impaired production of macrophage antimicrobial products and reduced expression of macrophage major histocompatibility complex class II antigens. IFN-γ-deficient mice were killed by a sublethal dose of the intracellular pathogen Mycobacterium bovis. Splenocytes exhibited uncontrolled proliferation in response to mitogen and alloantigen. After a mixed lymphocyte reaction, T cell cytolytic activity was enhanced against allogeneic target cells. Resting splenic natural killer cell activity was reduced in IFN-γ-deficient mice. Thus, IFN-γ is essential for the function of several cell types of the murine immune system.
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References
BANCROFT, G.J., TUMOR NECROSIS FACTOR IS INVOLVED IN THE T-CELL-INDEPENDENT PATHWAY OF MACROPHAGE ACTIVATION IN SCID MICE, JOURNAL OF IMMUNOLOGY 143: 127 (1989).
BENOIST, C, REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II GENES - X, Y AND OTHER LETTERS OF THE ALPHABET, ANNUAL REVIEW OF IMMUNOLOGY 8: 681 (1990).
BRENNAN, G.L., BIOTECHNIQUES 1: 78 (1983).
BUCHMEIER, N.A., REQUIREMENT OF ENDOGENOUS INTERFERON-GAMMA PRODUCTION FOR RESOLUTION OF LISTERIA-MONOCYTOGENES INFECTION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 82: 7404 (1985).
BUCY, R.P., LACK OF AN OBLIGATE ROLE FOR IFN-GAMMA IN THE PRIMARY INVITRO MIXED LYMPHOCYTE-RESPONSE, JOURNAL OF IMMUNOLOGY 140: 1148 (1988).
CRAWFORD, R.M., B-CELL STIMULATORY FACTOR-I (INTERLEUKIN-4) ACTIVATES MACROPHAGES FOR INCREASED TUMORICIDAL ACTIVITY AND EXPRESSION OF IA-ANTIGENS, JOURNAL OF IMMUNOLOGY 139: 135 (1987).
DALTON, D.K., unpublished data.
DING, A.H., RELEASE OF REACTIVE NITROGEN INTERMEDIATES AND REACTIVE OXYGEN INTERMEDIATES FROM MOUSE PERITONEAL-MACROPHAGES - COMPARISON OF ACTIVATING CYTOKINES AND EVIDENCE FOR INDEPENDENT PRODUCTION, JOURNAL OF IMMUNOLOGY 141: 2407 (1988).
DJEU, J.Y., POSITIVE SELF REGULATION OF CYTO-TOXICITY IN HUMAN NATURAL-KILLER CELLS BY PRODUCTION OF INTERFERON UPON EXPOSURE TO INFLUENZA AND HERPES VIRUSES, JOURNAL OF EXPERIMENTAL MEDICINE 156: 1222 (1982).
DJEU, J.Y., AUGMENTATION OF MOUSE NATURAL KILLER CELL ACTIVITY BY INTERFERON AND INTERFERON INDUCERS, JOURNAL OF IMMUNOLOGY 122: 175 (1979).
EZEKOWITZ, RAB, SURFACE-PROPERTIES OF BACILLUS CALMETTE-GUERIN-ACTIVATED MOUSE MACROPHAGES - REDUCED EXPRESSION OF MANNOSE-SPECIFIC ENDOCYTOSIS, FC-RECEPTORS, AND ANTIGEN F4-80 ACCOMPANIES INDUCTION OF IA, JOURNAL OF EXPERIMENTAL MEDICINE 154: 60 (1981).
GAJEWSKI, T.F., ANTI-PROLIFERATIVE EFFECT OF IFN-GAMMA IN IMMUNE REGULATION .1. IFN-GAMMA INHIBITS THE PROLIFERATION OF TH2 BUT NOT TH1 MURINE HELPER LYMPHOCYTE-T CLONES, JOURNAL OF IMMUNOLOGY 140: 4245 (1988).
GIDLUND, M, ENHANCED NK CELL ACTIVITY IN MICE INJECTED WITH INTERFERON AND INTERFERON INDUCERS, NATURE 273: 759 (1978).
GIOVARELLI, M, OBLIGATORY ROLE OF IFN-GAMMA IN INDUCTION OF LYMPHOKINE-ACTIVATED AND LYMPHOCYTE-T KILLER ACTIVITY, BUT NOT IN BOOSTING OF NATURAL CYTO-TOXICITY, JOURNAL OF IMMUNOLOGY 141: 2831 (1988).
GREEN, L.C., ANALYSIS OF NITRATE, NITRITE, AND [N-15]-LABELED NITRATE IN BIOLOGICAL-FLUIDS, ANALYTICAL BIOCHEMISTRY 126: 131 (1982).
HANDA, K, NATURAL-KILLER (NK) CELLS AS A RESPONDER TO INTERLEUKIN-2 (IL-2) .2. IL 2 INDUCED INTERFERON GAMMA-PRODUCTION, JOURNAL OF IMMUNOLOGY 130: 988 (1983).
KESHAV, S, LYSOZYME IS AN INDUCIBLE MARKER OF MACROPHAGE ACTIVATION IN MURINE TISSUES AS DEMONSTRATED BY INSITU HYBRIDIZATION, JOURNAL OF EXPERIMENTAL MEDICINE 174: 1049 (1991).
KIESSLING, R, NATURAL KILLER CELLS IN MOUSE .1. CYTOTOXIC CELLS WITH SPECIFICITY FOR MOUSE MOLONEY LEUKEMIA-CELLS - SPECIFICITY AND DISTRIBUTION ACCORDING TO GENOTYPE, EUROPEAN JOURNAL OF IMMUNOLOGY 5: 112 (1975).
KIRCHNER, H, PRODUCTION OF INTERFERON IN THE MURINE MIXED LYMPHOCYTE CULTURE .2. INTERFERON-PRODUCTION IS A T-CELL-DEPENDENT FUNCTION, INDEPENDENT OF PROLIFERATION, EUROPEAN JOURNAL OF IMMUNOLOGY 9: 824 (1979).
KOO, G.C., ESTABLISHMENT OF MONOCLONAL ANTI-NK-1.1 ANTIBODY, HYBRIDOMA 3: 301 (1984).
LIEW, F.Y., IMMUNOL TODAY 12: A17 (1991).
LIU, Y, JOURNAL OF EXPERIMENTAL MEDICINE 172: 1735 (1990).
MACKANESS, G.B., CELLULAR RESISTANCE TO INFECTION, JOURNAL OF EXPERIMENTAL MEDICINE 116: 381 (1962).
MCMAHON, A.P., THE WNT-1 (INT-1) PROTOONCOGENE IS REQUIRED FOR DEVELOPMENT OF A LARGE REGION OF THE MOUSE-BRAIN, CELL 62: 1073 (1990).
MORRISSEY, P.J., GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AUGMENTS THE PRIMARY ANTIBODY-RESPONSE BY ENHANCING THE FUNCTION OF ANTIGEN-PRESENTING CELLS, JOURNAL OF IMMUNOLOGY 139: 1113 (1987).
MURRAY, H.W., MACROPHAGE OXYGEN-DEPENDENT ANTI-MICROBIAL ACTIVITY .3. ENHANCED OXIDATIVE-METABOLISM AS AN EXPRESSION OF MACROPHAGE ACTIVATION, JOURNAL OF EXPERIMENTAL MEDICINE 152: 1596 (1980).
NATHAN, C.F., ROLE OF NITRIC-OXIDE SYNTHESIS IN MACROPHAGE ANTIMICROBIAL ACTIVITY, CURRENT OPINION IN IMMUNOLOGY 3: 65 (1991).
NATHAN, C.F., ACTIVATION OF HUMAN MACROPHAGES - COMPARISON OF OTHER CYTOKINES WITH INTERFERON-GAMMA, JOURNAL OF EXPERIMENTAL MEDICINE 160: 600 (1984).
PERUSSIA, B, INTERFERON-PRODUCTION BY HUMAN AND MURINE LYMPHOCYTES IN RESPONSE TO ALLOANTIGENS, JOURNAL OF IMMUNOLOGY 125: 1589 (1980).
RANGES, G.E., INHIBITION OF CYTOTOXIC T-CELL DEVELOPMENT BY TRANSFORMING GROWTH-FACTOR-BETA AND REVERSAL BY RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA, JOURNAL OF EXPERIMENTAL MEDICINE 166: 991 (1987).
REED, S.G., RECOMBINANT GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR ACTIVATES MACROPHAGES TO INHIBIT TRYPANOSOMA-CRUZI AND RELEASE HYDROGEN-PEROXIDE - COMPARISON WITH INTERFERON-GAMMA, JOURNAL OF EXPERIMENTAL MEDICINE 166: 1734 (1987).
Schreiber, R. D., Current Protocols in Immunology 1: CH6 (1991).
SCHREIBER, R.D., MONOCLONAL-ANTIBODIES TO MURINE GAMMA-INTERFERON WHICH DIFFERENTIALLY MODULATE MACROPHAGE ACTIVATION AND ANTIVIRAL ACTIVITY, JOURNAL OF IMMUNOLOGY 134: 1609 (1985).
SCHREIBER, R.D., LYMPHOKINES 11: 87 (1985).
Stein, M. L., Cytokines: A PracticalApproach: 245 (1991).
TRINCHIERI, G, IMMUNOLOGY TODAY 6: 131 (1985).
VILCEK, J, LYMPHOKINES 11: 1 (1985).
WALLICK, S.C., IMMUNOREGULATORY ROLE OF TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) IN DEVELOPMENT OF KILLER-CELLS - COMPARISON OF ACTIVE AND LATENT TGF-BETA-1, JOURNAL OF EXPERIMENTAL MEDICINE 172: 1777 (1990).
WEIGENT, D.A., INTERLEUKIN-2 ENHANCES NATURAL-KILLER CELL-ACTIVITY THROUGH INDUCTION OF GAMMA-INTERFERON, INFECTION AND IMMUNITY 41: 992 (1983).
WELSH, R.M., MOUSE NATURAL KILLER CELLS - INDUCTION SPECIFICITY, AND FUNCTION, JOURNAL OF IMMUNOLOGY 121: 1631 (1978).
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Volume 259 | Issue 5102
19 March 1993
19 March 1993
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- Dyana K. Dalton et al.
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