This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baumgarth, N. Articles by Kelso, A. Search for Related Content PubMed PubMed Citation Articles by Baumgarth, N. Articles by Kelso, A.

 Previous Article  |  Next Article 

J. Virol., 07 1996, 4411-4418, Vol 70, No. 7
Copyright © 1996, American Society for Microbiology

In vivo blockade of gamma interferon affects the influenza virus- induced humoral and the local cellular immune response in lung tissue

N Baumgarth and A Kelso
Cooperative Research Center for Vaccine Technology and Transplantation Biology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. nicoleB@qimr.edu.au

Influenza virus infection induces the local production of gamma interferon (IFN-gamma) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN- gamma by using monoclonal antibodies. Neutralization of IFN-gamma led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum but had little effect on other isotypes. Studies on cells isolated from the lung parenchyma itself revealed that at the height of the immune response the ability of these cells to produce cytokines after antigen or T-cell receptor/CD3 stimulation was not affected. Ex vivo cytolytic activity by lung parenchyma cells, which is induced by infection with this virus in normal mice, was also found to be undisturbed by this treatment, even though anti-IFN-gamma antibody activity was recovered from lung lavage samples and sera at all days studied. Surprisingly, in vivo neutralization of IFN-gamma led to a significant reduction in the magnitude of the cellular infiltrate in the lung tissue which followed infection, suggesting an involvement of IFN-gamma in the mechanisms that regulate increased leucocyte traffic in the inflamed lung parenchyma. This conclusion was supported by findings of differences between mock-treated and anti-IFN-gamma-treated mice in the number of CD8+ lung T cells expressing CD49d (alpha4- integrin) and CD62L at various times after influenza virus infection. This study therefore demonstrates that IFN-gamma affects the local cellular response in the respiratory tract as well as the systemic humoral response to influenza virus infection.

This article has been cited by other articles:

• Turner, S. J., Olivas, E., Gutierrez, A., Diaz, G., Doherty, P. C. (2007). Disregulated Influenza A Virus-Specific CD8+ T Cell Homeostasis in the Absence of IFN-{gamma} Signaling. J. Immunol. 178: 7616-7622 [Abstract] [Full Text]  
• Jayasekera, J. P., Vinuesa, C. G., Karupiah, G., King, N. J. C. (2006). Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice.. J. Gen. Virol. 87: 3361-3371 [Abstract] [Full Text]  
• Thanawongnuwech, R., Thacker, B., Halbur, P., Thacker, E. L. (2004). Increased Production of Proinflammatory Cytokines following Infection with Porcine Reproductive and Respiratory Syndrome Virus and Mycoplasma hyopneumoniae. CVI 11: 901-908 [Abstract] [Full Text]  
• La Gruta, N. L., Turner, S. J., Doherty, P. C. (2004). Hierarchies in Cytokine Expression Profiles for Acute and Resolving Influenza Virus-Specific CD8+ T Cell Responses: Correlation of Cytokine Profile and TCR Avidity. J. Immunol. 172: 5553-5560 [Abstract] [Full Text]  
• Johnson, B. J., Costelloe, E. O., Fitzpatrick, D. R., Haanen, J. B. A. G., Schumacher, T. N. M., Brown, L. E., Kelso, A. (2003). Single-cell perforin and granzyme expression reveals the anatomical localization of effector CD8+ T cells in influenza virus-infected mice. Proc. Natl. Acad. Sci. USA 100: 2657-2662 [Abstract] [Full Text]  
• Woodberry, T., Gardner, J., Elliott, S. L., Leyrer, S., Purdie, D. M., Chaplin, P., Suhrbier, A. (2003). Prime Boost Vaccination Strategies: CD8 T Cell Numbers, Protection, and Th1 Bias. J. Immunol. 170: 2599-2604 [Abstract] [Full Text]  
• Topham, D. J., Castrucci, M. R., Wingo, F. S., Belz, G. T., Doherty, P. C. (2001). The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8+ T Cells to the Lung During Influenza Pneumonia. J. Immunol. 167: 6983-6990 [Abstract] [Full Text]  
• Johnson, T. R., Fischer, J. E., Graham, B. S. (2001). Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine. J. Gen. Virol. 82: 2107-2116 [Abstract] [Full Text]  
• Galietta, L. J. V., Folli, C., Marchetti, C., Romano, L., Carpani, D., Conese, M., Zegarra-Moran, O. (2000). Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-gamma. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L1186-L1194 [Abstract] [Full Text]  
• Doyle, A. G., Buttigieg, K., Groves, P., Johnson, B. J., Kelso, A. (1999). The Activated Type 1-polarized CD8+ T Cell Population Isolated from an Effector Site Contains Cells with Flexible Cytokine Profiles. J. Exp. Med. 190: 1081-1092 [Abstract] [Full Text]  
• Ben-Yedidia, T., Marcus, H., Reisner, Y., Arnon, R. (1999). Intranasal administration of peptide vaccine protects human/mouse radiation chimera from influenza infection. Int Immunol 11: 1043-1051 [Abstract] [Full Text]  
• Baumgarth, N., Herman, O. C., Jager, G. C., Brown, L., Herzenberg, L. A., Herzenberg, L. A. (1999). Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system. Proc. Natl. Acad. Sci. USA 96: 2250-2255 [Abstract] [Full Text]  
• Parra, B., Hinton, D. R., Marten, N. W., Bergmann, C. C., Lin, M. T., Yang, C. S., Stohlman, S. A. (1999). IFN-{gamma} Is Required for Viral Clearance from Central Nervous System Oligodendroglia. J. Immunol. 162: 1641-1647 [Abstract] [Full Text]  
• Kyuwa, S., Tagawa, Y.-i., Shibata, S., Doi, K., Machii, K., Iwakura, Y. (1998). Murine Coronavirus-Induced Subacute Fatal Peritonitis in C57BL/6 Mice Deficient in Gamma Interferon. J. Virol. 72: 9286-9290 [Abstract] [Full Text]  
• Karupiah, G., Chen, J.-H., Mahalingam, S., Nathan, C. F., MacMicking, J. D. (1998). Rapid Interferon gamma -dependent Clearance of Influenza A Virus and Protection from Consolidating Pneumonitis in Nitric Oxide Synthase 2-deficient Mice. J. Exp. Med. 188: 1541-1546 [Abstract] [Full Text]  
• Moskophidis, D., Kioussis, D. (1998). Contribution of  Virus-specific CD8+ Cytotoxic T Cells to Virus Clearance or Pathologic Manifestations of Influenza Virus Infection in a T Cell Receptor Transgenic Mouse Model. J. Exp. Med. 188: 223-232 [Abstract] [Full Text]  
• Thomson, S. A., Sherritt, M. A., Medveczky, J., Elliott, S. L., Moss, D. J., Fernando, G. J. P., Brown, L. E., Suhrbier, A. (1998). Delivery of Multiple CD8 Cytotoxic T Cell Epitopes by DNA Vaccination. J. Immunol. 160: 1717-1723 [Abstract] [Full Text]  
• Adler, H., Beland, J. L., Del-Pan, N. C., Kobzik, L., Brewer, J. P., Martin, T. R., Rimm, I. J. (1997). Suppression of Herpes Simplex Virus Type 1 (HSV-1)-induced Pneumonia in Mice by Inhibition of Inducible Nitric Oxide Synthase (iNOS, NOS2). J. Exp. Med. 185: 1533-1540 [Abstract] [Full Text]