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. 1995 Sep;69(9):5592–5598. doi: 10.1128/jvi.69.9.5592-5598.1995

Differential antigen burden modulates the gamma interferon but not the immunoglobulin response in mice that vary in susceptibility to Sendai virus pneumonia.

X Y Mo 1, M Sangster 1, S Sarawar 1, C Coleclough 1, P C Doherty 1
PMCID: PMC189415  PMID: 7637005

Abstract

Sendai virus, a paramyxovirus which causes murine pneumonia, grew to approximately 10-fold higher titers and was cleared less rapidly from the lungs of 129/J (129) than H-2b-compatible C57BL/6J (B6) mice. The more susceptible 129 mice also made higher titers of gamma interferon (IFN-gamma) and immunoglobulin G2a (IgG2a) virus-specific antibody. Analysis with acutely irradiated (950 rads) mice and immunologically reconstituted bone marrow (BM) radiation chimeras indicated that the enhanced virus growth was a function of the radiation-resistant respiratory epithelium. Prolonged exposure to more virus in turn influenced the magnitude of IFN-gamma production, most of which was made by CD4+ T lymphocytes. Somewhat surprisingly, however, the 129 pattern of a higher virus-specific serum Ig response skewed towards IgG2a mapped to the reconstituting BM. Thus, the characteristics of the humoral response are at least partly dissociated from both the antigen load, resulting from viral replication, and the level of IFN-gamma production. Further analysis of double chimeras (B6+129 BM-->B6 recipients) confirmed that the divergent humoral immune response to Sendai virus in B6 and 129 mice is largely determined by the inherent characteristics of the lymphoid cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Breider M. A., Adams L. G., Womack J. E. Influence of interferon in natural resistance of mice to Sendai virus pneumonia. Am J Vet Res. 1987 Dec;48(12):1746–1750. [PubMed] [Google Scholar]
  3. Brodeur P. H., Riblet R. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur J Immunol. 1984 Oct;14(10):922–930. doi: 10.1002/eji.1830141012. [DOI] [PubMed] [Google Scholar]
  4. Brownstein D. G. Resistance/susceptibility to lethal Sendai virus infection genetically linked to a mucociliary transport polymorphism. J Virol. 1987 May;61(5):1670–1671. doi: 10.1128/jvi.61.5.1670-1671.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brownstein D. G., Smith A. L., Johnson E. A. Sendai virus infection in genetically resistant and susceptible mice. Am J Pathol. 1981 Nov;105(2):156–163. [PMC free article] [PubMed] [Google Scholar]
  6. Brownstein D. G., Winkler S. Genetic determinants of lung virus titers and resistance to lethal Sendai virus pneumonia. Arch Virol. 1987;96(3-4):201–214. doi: 10.1007/BF01320960. [DOI] [PubMed] [Google Scholar]
  7. Cole G. A., Katz J. M., Hogg T. L., Ryan K. W., Portner A., Woodland D. L. Analysis of the primary T-cell response to Sendai virus infection in C57BL/6 mice: CD4+ T-cell recognition is directed predominantly to the hemagglutinin-neuraminidase glycoprotein. J Virol. 1994 Nov;68(11):6863–6870. doi: 10.1128/jvi.68.11.6863-6870.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dales S., Fujinami R. S., Oldstone M. B. Infection with vaccinia favors the selection of hybridomas synthesizing autoantibodies against intermediate filaments, one of them cross-reacting with the virus hemagglutinin. J Immunol. 1983 Sep;131(3):1546–1553. [PubMed] [Google Scholar]
  9. Doherty P. C., Allan J. E., Lynch F., Ceredig R. Dissection of an inflammatory process induced by CD8+ T cells. Immunol Today. 1990 Feb;11(2):55–59. doi: 10.1016/0167-5699(90)90019-6. [DOI] [PubMed] [Google Scholar]
  10. Doherty P. C., Allan W., Eichelberger M., Carding S. R. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Annu Rev Immunol. 1992;10:123–151. doi: 10.1146/annurev.iy.10.040192.001011. [DOI] [PubMed] [Google Scholar]
  11. Doherty P. C., Ceredig R., Allan J. E. Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology. Clin Immunol Immunopathol. 1988 Apr;47(1):19–26. doi: 10.1016/0090-1229(88)90141-9. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Fujinami R. S., Oldstone M. B. Molecular mimicry as a mechanism for virus-induced autoimmunity. Immunol Res. 1989;8(1):3–15. doi: 10.1007/BF02918552. [DOI] [PubMed] [Google Scholar]
  15. Gessner A., Drjupin R., Löhler J., Lother H., Lehmann-Grube F. IFN-gamma production in tissues of mice during acute infection with lymphocytic choriomeningitis virus. J Immunol. 1990 Apr 15;144(8):3160–3165. [PubMed] [Google Scholar]
  16. Gessner A., Moskophidis D., Lehmann-Grube F. Enumeration of single IFN-gamma-producing cells in mice during viral and bacterial infection. J Immunol. 1989 Feb 15;142(4):1293–1298. [PubMed] [Google Scholar]
  17. Halpern M. D., Fisher C. L., Cohen P. L., Eisenberg R. A. Influence of the Ig H chain locus on autoantibody production in autoimmune mice. J Immunol. 1992 Dec 1;149(11):3735–3740. [PubMed] [Google Scholar]
  18. 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]
  19. Hou S., Doherty P. C. Partitioning of responder CD8+ T cells in lymph node and lung of mice with Sendai virus pneumonia by LECAM-1 and CD45RB phenotype. J Immunol. 1993 Jun 15;150(12):5494–5500. [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Hyland L., Hou S., Coleclough C., Takimoto T., Doherty P. C. Mice lacking CD8+ T cells develop greater numbers of IgA-producing cells in response to a respiratory virus infection. Virology. 1994 Oct;204(1):234–241. doi: 10.1006/viro.1994.1527. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Jones P. D., Ada G. L. Influenza virus-specific antibody-secreting cells in the murine lung during primary influenza virus infection. J Virol. 1986 Nov;60(2):614–619. doi: 10.1128/jvi.60.2.614-619.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Korngold R., Feldman A., Rorke L. B., Lublin F. D., Doherty P. C. Acute experimental allergic encephalomyelitis in radiation bone marrow chimeras between high and low susceptible strains of mice. Immunogenetics. 1986;24(5):309–315. doi: 10.1007/BF00395536. [DOI] [PubMed] [Google Scholar]
  26. Kuppers R. C., Epstein L. D., Outschoorn I. M., Rose N. R. The IgG2a antibody response to thyroglobulin is linked to the Igh locus in mouse. Immunogenetics. 1994;39(6):404–411. doi: 10.1007/BF00176157. [DOI] [PubMed] [Google Scholar]
  27. Lublin F. D., Knobler R. L., Doherty P. C., Korngold R. Relapsing experimental allergic encephalomyelitis in radiation bone marrow chimeras between high and low susceptible strains of mice. Clin Exp Immunol. 1986 Dec;66(3):491–496. [PMC free article] [PubMed] [Google Scholar]
  28. Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mackay I. R., Wittingham S., Tait B. Genetic control of immune responsiveness in man. Vox Sang. 1977;32(1):10–19. doi: 10.1111/j.1423-0410.1977.tb00598.x. [DOI] [PubMed] [Google Scholar]
  30. Majlessi L., Benaroch P., Denoyelle C., Bordenave G. Role of CD4+ and CD8+ cell subsets during amplification of natural T cell activity against IgG2ab in Igha mice and during induction of IgG2ab allotype suppression in Igha/b mice. J Immunol. 1993 Aug 15;151(4):1859–1867. [PubMed] [Google Scholar]
  31. Majlessi L., Marcos M. A., Benaroch P., Denoyelle C., Bordenave G. T cell-induced Ig allotypic suppression in mice. Basis for emergence or tolerization, during the perinatal period, of natural T cells specific to the IgG2ab allotype. J Immunol. 1994 Apr 1;152(7):3342–3352. [PubMed] [Google Scholar]
  32. McWilliam A. S., Nelson D., Thomas J. A., Holt P. G. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces. J Exp Med. 1994 Apr 1;179(4):1331–1336. doi: 10.1084/jem.179.4.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Miller R. A., Reiss C. S. Limiting dilution cultures reveal latent influenza virus-specific helper T cells in virus-primed mice. J Mol Cell Immunol. 1984;1(6):357–368. [PubMed] [Google Scholar]
  34. 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]
  35. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  36. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Parker J. C., Whiteman M. D., Richter C. B. Susceptibility of inbred and outbred mouse strains to Sendai virus and prevalence of infection in laboratory rodents. Infect Immun. 1978 Jan;19(1):123–130. doi: 10.1128/iai.19.1.123-130.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pavlovic J., Haller O., Staeheli P. Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. J Virol. 1992 Apr;66(4):2564–2569. doi: 10.1128/jvi.66.4.2564-2569.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Portner A., Scroggs R. A., Metzger D. W. Distinct functions of antigenic sites of the HN glycoprotein of Sendai virus. Virology. 1987 May;158(1):61–68. doi: 10.1016/0042-6822(87)90238-8. [DOI] [PubMed] [Google Scholar]
  40. Punnonen J., de Vries J. E. IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature human fetal B cells. J Immunol. 1994 Feb 1;152(3):1094–1102. [PubMed] [Google Scholar]
  41. Sakaguchi T., Takao S., Kiyotani K., Fujii Y., Nakayama T., Yoshida T. Expression of the HN, F, NP and M proteins of Sendai virus by recombinant vaccinia viruses and their contribution to protective immunity against Sendai virus infections in mice. J Gen Virol. 1993 Mar;74(Pt 3):479–484. doi: 10.1099/0022-1317-74-3-479. [DOI] [PubMed] [Google Scholar]
  42. 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]
  43. Sarawar S. R., Blackman M. A., Doherty P. C. Superantigen shock in mice with an inapparent viral infection. J Infect Dis. 1994 Nov;170(5):1189–1194. doi: 10.1093/infdis/170.5.1189. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. 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]
  47. Shalaby M. R., Halgunset J., Haugen O. A., Aarset H., Aarden L., Waage A., Matsushima K., Kvithyll H., Boraschi D., Lamvik J. Cytokine-associated tissue injury and lethality in mice: a comparative study. Clin Immunol Immunopathol. 1991 Oct;61(1):69–82. doi: 10.1016/s0090-1229(06)80008-5. [DOI] [PubMed] [Google Scholar]
  48. Snapper C. M., Peschel C., Paul W. E. IFN-gamma stimulates IgG2a secretion by murine B cells stimulated with bacterial lipopolysaccharide. J Immunol. 1988 Apr 1;140(7):2121–2127. [PubMed] [Google Scholar]
  49. Tashiro M., Homma M. Protection of mice from wild-type Sendai virus infection by a trypsin-resistant mutant, TR-2. J Virol. 1985 Jan;53(1):228–234. doi: 10.1128/jvi.53.1.228-234.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Tashiro M., Seto J. T., Klenk H. D., Rott R. Possible involvement of microtubule disruption in bipolar budding of a Sendai virus mutant, F1-R, in epithelial MDCK cells. J Virol. 1993 Oct;67(10):5902–5910. doi: 10.1128/jvi.67.10.5902-5910.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Taylor P. M., Meager A., Askonas B. A. Influenza virus-specific T cells lead to early interferon gamma in lungs of infected hosts: development of a sensitive radioimmunoassay. J Gen Virol. 1989 Apr;70(Pt 4):975–978. doi: 10.1099/0022-1317-70-4-975. [DOI] [PubMed] [Google Scholar]

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