Abstract
Interferon gamma (IFN-gamma) is a pleiotropic cytokine secreted by T lymphocytes and natural killer (NK) cells and has been noted to be a first line of host defense in the control of viral infections. To examine further the role of this cytokine in the control of viral infections, mice with a targeted mutation in the IFN-gamma gene were infected with influenza virus, and the in vivo antibody and cell- mediated immune response to viral infection were examined. In addition, cell lines and clones were derived from the immunized animals and the in vitro cytokine production and cytotoxic T lymphocyte (CTL) response were analyzed. The absence of IFN-gamma led to increased production of influenza-specific IgG1, IL-4, and IL-5 as compared to wild-type littermate control animals. In contrast, there was no difference noted in the development of an effective CTL response between IFN-gamma- deficient and wild-type animals. In this model of experimental influenza infection, IFN-gamma is not necessary for the development of an effective humoral or cellular immune response to challenge with this respiratory virus.
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- Bastin J., Rothbard J., Davey J., Jones I., Townsend A. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. J Exp Med. 1987 Jun 1;165(6):1508–1523. doi: 10.1084/jem.165.6.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braciale T. J., Andrew M. E., Braciale V. L. Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes. J Exp Med. 1981 Apr 1;153(4):910–923. doi: 10.1084/jem.153.4.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braciale T. J. Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes. Cell Immunol. 1977 Oct;33(2):423–436. doi: 10.1016/0008-8749(77)90170-8. [DOI] [PubMed] [Google Scholar]
- Bucy R. P., Hanto D. W., Berens E., Schreiber R. D. Lack of an obligate role for IFN-gamma in the primary in vitro mixed lymphocyte response. J Immunol. 1988 Feb 15;140(4):1148–1152. [PubMed] [Google Scholar]
- Dalton D. K., Pitts-Meek S., Keshav S., Figari I. S., Bradley A., Stewart T. A. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science. 1993 Mar 19;259(5102):1739–1742. doi: 10.1126/science.8456300. [DOI] [PubMed] [Google Scholar]
- Erard F., Corthesy P., Nabholz M., Lowenthal J. W., Zaech P., Plaetinck G., MacDonald H. R. Interleukin 2 is both necessary and sufficient for the growth and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. J Immunol. 1985 Mar;134(3):1644–1652. [PubMed] [Google Scholar]
- Fellous M., Nir U., Wallach D., Merlin G., Rubinstein M., Revel M. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3082–3086. doi: 10.1073/pnas.79.10.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finkelman F. D., Katona I. M., Mosmann T. R., Coffman R. L. IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol. 1988 Feb 15;140(4):1022–1027. [PubMed] [Google Scholar]
- Huang S., Hendriks W., Althage A., Hemmi S., Bluethmann H., Kamijo R., Vilcek J., Zinkernagel R. M., Aguet M. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742–1745. doi: 10.1126/science.8456301. [DOI] [PubMed] [Google Scholar]
- Klein J. R., Raulet D. H., Pasternack M. S., Bevan M. J. Cytotoxic T lymphocytes produce immune interferon in response to antigen or mitogen. J Exp Med. 1982 Apr 1;155(4):1198–1203. doi: 10.1084/jem.155.4.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
- Kühn R., Rajewsky K., Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991 Nov 1;254(5032):707–710. doi: 10.1126/science.1948049. [DOI] [PubMed] [Google Scholar]
- Lin Y. L., Askonas B. A. Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. J Exp Med. 1981 Aug 1;154(2):225–234. doi: 10.1084/jem.154.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez A. F., Elliott M. J., Woodcock J., Vadas M. A. GM-CSF, IL-3 and IL-5: cross-competition on human haemopoietic cells. Immunol Today. 1992 Dec;13(12):495–500. doi: 10.1016/0167-5699(92)90025-3. [DOI] [PubMed] [Google Scholar]
- Lukacher A. E., Braciale V. L., Braciale T. J. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 1;160(3):814–826. doi: 10.1084/jem.160.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maraskovsky E., Chen W. F., Shortman K. IL-2 and IFN-gamma are two necessary lymphokines in the development of cytolytic T cells. J Immunol. 1989 Aug 15;143(4):1210–1214. [PubMed] [Google Scholar]
- Morris A. G., Lin Y. L., Askonas B. A. Immune interferon release when a cloned cytotoxic T-cell line meets its correct influenza-infected target cell. Nature. 1982 Jan 14;295(5845):150–152. doi: 10.1038/295150a0. [DOI] [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
- Restifo N. P., Esquivel F., Kawakami Y., Yewdell J. W., Mulé J. J., Rosenberg S. A., Bennink J. R. Identification of human cancers deficient in antigen processing. J Exp Med. 1993 Feb 1;177(2):265–272. doi: 10.1084/jem.177.2.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scherle P. A., Gerhard W. Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J Exp Med. 1986 Oct 1;164(4):1114–1128. doi: 10.1084/jem.164.4.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schorle H., Holtschke T., Hünig T., Schimpl A., Horak I. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting. Nature. 1991 Aug 15;352(6336):621–624. doi: 10.1038/352621a0. [DOI] [PubMed] [Google Scholar]
- Simon M. M., Hochgeschwender U., Brugger U., Landolfo S. Monoclonal antibodies to interferon-gamma inhibit interleukin 2-dependent induction of growth and maturation in lectin/antigen-reactive cytolytic T lymphocyte precursors. J Immunol. 1986 Apr 15;136(8):2755–2762. [PubMed] [Google Scholar]
- Solari R. Identification and distribution of two forms of the interleukin 1 receptor. Cytokine. 1990 Jan;2(1):21–28. doi: 10.1016/1043-4666(90)90039-v. [DOI] [PubMed] [Google Scholar]
- Stevens T. L., Bossie A., Sanders V. M., Fernandez-Botran R., Coffman R. L., Mosmann T. R., Vitetta E. S. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature. 1988 Jul 21;334(6179):255–258. doi: 10.1038/334255a0. [DOI] [PubMed] [Google Scholar]
- Taylor P. M., Askonas B. A. Diversity in the biological properties of anti-influenza cytotoxic T cell clones. Eur J Immunol. 1983 Sep;13(9):707–711. doi: 10.1002/eji.1830130904. [DOI] [PubMed] [Google Scholar]
- Taylor P. M., Esquivel F., Askonas B. A. Murine CD4+ T cell clones vary in function in vitro and in influenza infection in vivo. Int Immunol. 1990;2(4):323–328. doi: 10.1093/intimm/2.4.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trenn G., Takayama H., Hu-Li J., Paul W. E., Sitkovsky M. V. B cell stimulatory factor 1 (IL-4) enhances the development of cytotoxic T cells from Lyt-2+ resting murine T lymphocytes. J Immunol. 1988 Feb 15;140(4):1101–1106. [PubMed] [Google Scholar]
- Widmer M. B., Grabstein K. H. Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Nature. 1987 Apr 23;326(6115):795–798. doi: 10.1038/326795a0. [DOI] [PubMed] [Google Scholar]
- Yang Y., Waters J. B., Früh K., Peterson P. A. Proteasomes are regulated by interferon gamma: implications for antigen processing. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4928–4932. doi: 10.1073/pnas.89.11.4928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yap K. L., Ada G. L. Cytotoxic T cells in the lungs of mice infected with an influenza A virus. Scand J Immunol. 1978;7(1):73–80. doi: 10.1111/j.1365-3083.1978.tb00428.x. [DOI] [PubMed] [Google Scholar]
- Yap K. L., Ada G. L. The recovery of mice from influenza virus infection: adoptive transfer of immunity with immune T lymphocytes. Scand J Immunol. 1978;7(5):389–397. doi: 10.1111/j.1365-3083.1978.tb00469.x. [DOI] [PubMed] [Google Scholar]
- Yap K. L., Braciale T. J., Ada G. L. Role of T-cell function in recovery from murine influenza infection. Cell Immunol. 1979 Mar 15;43(2):341–351. doi: 10.1016/0008-8749(79)90178-3. [DOI] [PubMed] [Google Scholar]
