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. 1997 Mar;71(3):1906–1910. doi: 10.1128/jvi.71.3.1906-1910.1997

The cytotoxic T-lymphocyte response to Sendai virus is unimpaired in the absence of gamma interferon.

X Y Mo 1, R A Tripp 1, M Y Sangster 1, P C Doherty 1
PMCID: PMC191265  PMID: 9032321

Abstract

Sendai virus is eliminated from the respiratory tract of gamma interferon (IFN-gamma) -/- BALB/c mice with normal kinetics. The level of virus-specific cytotoxic T-lymphocyte (CTL) activity in the cell population recovered by bronchoalveolar lavage is unimpaired, the prevalence of interleukin-4 (IL-4)-producing cells is increased, and the titers of virus-specific immunoglobulins IgG1 and IgG2b are higher in the IFN-gamma -/- mice. The emergence of this T-helper 2 response profile in both lymphoid tissue and the pneumonic lung has no obvious deleterious consequences. Virus clearance is slightly delayed following depletion of the CD4+ subset, with the effect being similar in magnitude for IFN-gamma -/- and +/+ mice. However, the generation of CTL precursors (CTLp) is diminished in the IFN-gamma -/- (but not +/+) mice in the absence of concurrent CD4+ T help. Apparently the clonal expansion of the CTLp population can be promoted either by a cytokine (perhaps IL-2) produced by the IFN-gamma -/- CD4+ T cells or by IFN-gamma made by other cell types in the +/+ mice.

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Selected References

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  1. Allan W., Tabi Z., Cleary A., Doherty P. C. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol. 1990 May 15;144(10):3980–3986. [PubMed] [Google Scholar]
  2. Baumgarth N., Kelso A. In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue. J Virol. 1996 Jul;70(7):4411–4418. doi: 10.1128/jvi.70.7.4411-4418.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carding S. R., Allan W., McMickle A., Doherty P. C. Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. J Exp Med. 1993 Feb 1;177(2):475–482. doi: 10.1084/jem.177.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cherwinski H. M., Schumacher J. H., Brown K. D., Mosmann T. R. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies. J Exp Med. 1987 Nov 1;166(5):1229–1244. doi: 10.1084/jem.166.5.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cooper A. M., Dalton D. K., Stewart T. A., Griffin J. P., Russell D. G., Orme I. M. Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med. 1993 Dec 1;178(6):2243–2247. doi: 10.1084/jem.178.6.2243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  8. Farrar M. A., Schreiber R. D. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol. 1993;11:571–611. doi: 10.1146/annurev.iy.11.040193.003035. [DOI] [PubMed] [Google Scholar]
  9. Fujihashi K., McGhee J. R., Beagley K. W., McPherson D. T., McPherson S. A., Huang C. M., Kiyono H. Cytokine-specific ELISPOT assay. Single cell analysis of IL-2, IL-4 and IL-6 producing cells. J Immunol Methods. 1993 Apr 2;160(2):181–189. doi: 10.1016/0022-1759(93)90176-8. [DOI] [PubMed] [Google Scholar]
  10. Graham M. B., Dalton D. K., Giltinan D., Braciale V. L., Stewart T. A., Braciale T. J. Response to influenza infection in mice with a targeted disruption in the interferon gamma gene. J Exp Med. 1993 Nov 1;178(5):1725–1732. doi: 10.1084/jem.178.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
  12. Harris N., Buller R. M., Karupiah G. Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication. J Virol. 1995 Feb;69(2):910–915. doi: 10.1128/jvi.69.2.910-915.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hou S., Doherty P. C. Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus-infected epithelium. Eur J Immunol. 1995 Jan;25(1):111–116. doi: 10.1002/eji.1830250120. [DOI] [PubMed] [Google Scholar]
  14. Hou S., Doherty P. C., Zijlstra M., Jaenisch R., Katz J. M. Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. J Immunol. 1992 Aug 15;149(4):1319–1325. [PubMed] [Google Scholar]
  15. Hou S., Mo X. Y., Hyland L., Doherty P. C. Host response to Sendai virus in mice lacking class II major histocompatibility complex glycoproteins. J Virol. 1995 Mar;69(3):1429–1434. doi: 10.1128/jvi.69.3.1429-1434.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hyland L., Sangster M., Sealy R., Coleclough C. Respiratory virus infection of mice provokes a permanent humoral immune response. J Virol. 1994 Sep;68(9):6083–6086. doi: 10.1128/jvi.68.9.6083-6086.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karupiah G., Fredrickson T. N., Holmes K. L., Khairallah L. H., Buller R. M. Importance of interferons in recovery from mousepox. J Virol. 1993 Jul;67(7):4214–4226. doi: 10.1128/jvi.67.7.4214-4226.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kelso A. Frequency analysis of lymphokine-secreting CD4+ and CD8+ T cells activated in a graft-versus-host reaction. J Immunol. 1990 Oct 1;145(7):2167–2176. [PubMed] [Google Scholar]
  19. Landolfo S., Gariglio M., Gribaudo G., Jemma C., Giovarelli M., Cavallo G. Interferon-gamma is not an antiviral, but a growth-promoting factor for T lymphocytes. Eur J Immunol. 1988 Apr;18(4):503–509. doi: 10.1002/eji.1830180403. [DOI] [PubMed] [Google Scholar]
  20. Locksley R. M., Scott P. Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. Immunol Today. 1991 Mar;12(3):A58–A61. doi: 10.1016/S0167-5699(05)80017-9. [DOI] [PubMed] [Google Scholar]
  21. Mo X. Y., Sangster M., Sarawar S., Coleclough C., Doherty P. C. Differential antigen burden modulates the gamma interferon but not the immunoglobulin response in mice that vary in susceptibility to Sendai virus pneumonia. J Virol. 1995 Sep;69(9):5592–5598. doi: 10.1128/jvi.69.9.5592-5598.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mo X. Y., Sarawar S. R., Doherty P. C. Induction of cytokines in mice with parainfluenza pneumonia. J Virol. 1995 Feb;69(2):1288–1291. doi: 10.1128/jvi.69.2.1288-1291.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Mosmann T. R., Coffman R. L. Heterogeneity of cytokine secretion patterns and functions of helper T cells. Adv Immunol. 1989;46:111–147. doi: 10.1016/s0065-2776(08)60652-5. [DOI] [PubMed] [Google Scholar]
  25. Mosmann T. R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138–146. doi: 10.1016/0167-5699(96)80606-2. [DOI] [PubMed] [Google Scholar]
  26. Müller U., Steinhoff U., Reis L. F., Hemmi S., Pavlovic J., Zinkernagel R. M., Aguet M. Functional role of type I and type II interferons in antiviral defense. Science. 1994 Jun 24;264(5167):1918–1921. doi: 10.1126/science.8009221. [DOI] [PubMed] [Google Scholar]
  27. Portner A., Marx P. A., Kingsbury D. W. Isolation and characterization of Sendai virus temperature-sensitive mutants. J Virol. 1974 Feb;13(2):298–304. doi: 10.1128/jvi.13.2.298-304.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sangster M., Hyland L., Sealy R., Coleclough C. Distinctive kinetics of the antibody-forming cell response to Sendai virus infection of mice in different anatomical compartments. Virology. 1995 Feb 20;207(1):287–291. doi: 10.1006/viro.1995.1079. [DOI] [PubMed] [Google Scholar]
  29. Sarawar S. R., Carding S. R., Allan W., McMickle A., Fujihashi K., Kiyono H., McGhee J. R., Doherty P. C. Cytokine profiles of bronchoalveolar lavage cells from mice with influenza pneumonia: consequences of CD4+ and CD8+ T cell depletion. Reg Immunol. 1993 May-Aug;5(3-4):142–150. [PubMed] [Google Scholar]
  30. Sarawar S. R., Doherty P. C. Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. J Virol. 1994 May;68(5):3112–3119. doi: 10.1128/jvi.68.5.3112-3119.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sarawar S. R., Sangster M., Coffman R. L., Doherty P. C. Administration of anti-IFN-gamma antibody to beta 2-microglobulin-deficient mice delays influenza virus clearance but does not switch the response to a T helper cell 2 phenotype. J Immunol. 1994 Aug 1;153(3):1246–1253. [PubMed] [Google Scholar]
  32. Sibille C., Gould K. G., Willard-Gallo K., Thomson S., Rivett A. J., Powis S., Butcher G. W., De Baetselier P. LMP2+ proteasomes are required for the presentation of specific antigens to cytotoxic T lymphocytes. Curr Biol. 1995 Aug 1;5(8):923–930. doi: 10.1016/s0960-9822(95)00182-5. [DOI] [PubMed] [Google Scholar]
  33. Snapper C. M., Mond J. J. Towards a comprehensive view of immunoglobulin class switching. Immunol Today. 1993 Jan;14(1):15–17. doi: 10.1016/0167-5699(93)90318-F. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Suda T., Sato A., Sugiura W., Chida K. Induction of MHC class II antigens on rat bronchial epithelial cells by interferon-gamma and its effect on antigen presentation. Lung. 1995;173(2):127–137. doi: 10.1007/BF02981472. [DOI] [PubMed] [Google Scholar]
  36. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
  37. Tripp R. A., Hou S., Doherty P. C. Temporal loss of the activated L-selectin-low phenotype for virus-specific CD8+ memory T cells. J Immunol. 1995 Jun 1;154(11):5870–5875. [PubMed] [Google Scholar]
  38. Tripp R. A., Hou S., McMickle A., Houston J., Doherty P. C. Recruitment and proliferation of CD8+ T cells in respiratory virus infections. J Immunol. 1995 Jun 1;154(11):6013–6021. [PubMed] [Google Scholar]
  39. Tripp R. A., Sarawar S. R., Doherty P. C. Characteristics of the influenza virus-specific CD8+ T cell response in mice homozygous for disruption of the H-2lAb gene. J Immunol. 1995 Sep 15;155(6):2955–2959. [PubMed] [Google Scholar]
  40. Wong G. H., Clark-Lewis I., Harris A. W., Schrader J. W. Effect of cloned interferon-gamma on expression of H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin. Eur J Immunol. 1984 Jan;14(1):52–56. doi: 10.1002/eji.1830140110. [DOI] [PubMed] [Google Scholar]
  41. van den Broek M. F., Müller U., Huang S., Aguet M., Zinkernagel R. M. Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. J Virol. 1995 Aug;69(8):4792–4796. doi: 10.1128/jvi.69.8.4792-4796.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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