1887

Abstract

The SAM-P1 strain of senescence-accelerated model mice shows an impaired T helper type 1 (Th1) immune response upon infection with influenza virus, which results in high susceptibility to the virus. Treatment of spleen cells from SAM-P1 mice with an immunostimulatory oligodeoxynucleotide containing a cytidine-guanosine motif (CpG ODN) increased the ratio of the titre of IFN- to that of IL-4. Administration of CpG ODN to SAM-P1 mice generated satisfactory virus-specific cytotoxic T-lymphocyte responses and natural killer cell activation and the virus-specific immunoglobulin (Ig) isotype switched from IgG1 to IgG2a. Virus growth in the lungs of CpG ODN-treated SAM-P1 mice was cleared quickly and mice survived the lethal influenza virus infection. It could be inferred that a possible mechanism of CpG ODN for normalization of senescence-associated dysregulation of the Th1/Th2 balance involves the upregulated expression of CD154 and CD40 molecules on immune-competent cells. These results suggest that CpG ODN could contribute to the development of a protective strategy against infectious diseases, especially among immunocompromised elderly persons, by stimulating Th1 immune responses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19029-0
2003-06-01
2020-08-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/6/vir841623.html?itemId=/content/journal/jgv/10.1099/vir.0.19029-0&mimeType=html&fmt=ahah

References

  1. Bender B. S., Johnson M. P., Small P. A.. 1991; Influenza in senescent mice: impaired cytotoxic T-lymphocyte activity is correlated with prolonged infection. Immunology72:514–519
    [Google Scholar]
  2. Brazolot Millan C. L., Weeratna R., Krieg A. M., Siegrist C. A., Davis H. L.. 1998; CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice. Proc Natl Acad Sci U S A95:15553–15558
    [Google Scholar]
  3. Cella M., Scheidegger D., Palmer-Lehmann K., Lane P., Lanzavecchia A., Alber G.. 1996; Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med184:747–752
    [Google Scholar]
  4. Cho H. J., Takabayashi K., Cheng P. M., Nguyen M. D., Corr M., Tuck S., Raz E.. 2000; Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism. Nat Biotechnol18:509–514
    [Google Scholar]
  5. Chu R. S., Targoni O. S., Krieg A. M., Lehmann P. V., Harding C. V.. 1997; CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity. J Exp Med186:1623–1631
    [Google Scholar]
  6. Davis H. L.. 2000; Use of CpG DNA for enhancing specific immune responses. Curr Top Microbiol Immunol247:171–183
    [Google Scholar]
  7. Decker T., Lohmann-Matthes M. L.. 1988; A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods115:61–69
    [Google Scholar]
  8. Dong L., Mori I., Hossain Md. J., Kimura Y.. 2000; The senescence-accelerated mouse shows aging-related defects in cellular but not humoral immunity against influenza virus infection. J Infect Dis182:391–396
    [Google Scholar]
  9. Gardner E. M., Murasko D. M.. 2002; Age-related changes in type 1 and type 2 cytokine production in humans. Biogerontology3:271–289
    [Google Scholar]
  10. Gibbons R. J.. 1992; How microorganisms cause diseases. In Infectious Diseases pp 7–106 Edited by Gorbach S. L., Bartlett J. G., Blacklow N. R.. Philadelphia: WB Saunders;
    [Google Scholar]
  11. Hacker H., Mischak H., Miethke T., Liptay S., Schmid R., Sparwasser T., Heeg K., Lipford G. B., Wagner H.. 1998; CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation. EMBO J17:6230–6240
    [Google Scholar]
  12. Hartmann G., Krieg A. M.. 2000; Mechanism and function of a newly identified CpG DNA motif in human primary B cells. J Immunol164:944–953
    [Google Scholar]
  13. Haruna H., Inaba M., Inaba K.. 7 other authors 1995; Abnormalities of B cells and dendritic cells in SAMP1 mice. Eur J Immunol25:1319–1325
    [Google Scholar]
  14. Krieg A. M., Matson S., Fisher E.. 1996; Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs. Antisense Nucleic Acid Drug Dev6:133–139
    [Google Scholar]
  15. Mannon R. B., Nataraj C., Pisetsky D. S.. 2000; Stimulation of thymocyte proliferation by phosphorothioate DNA oligonucleotides. Cell Immunol201:14–21
    [Google Scholar]
  16. Miller R. A.. 1996; The aging immune system: primer and prospectus. Science273:70–74
    [Google Scholar]
  17. Minutello M., Senatore F., Cecchinelli G., Bianchi M., Andreani T., Podda A., Crovari P.. 1999; Safety and immunogenicity of an inactivated subunit influenza virus vaccine combined with MF59 adjuvant emulsion in elderly subjects, immunized for three consecutive influenza seasons. Vaccine17:99–104
    [Google Scholar]
  18. Monteiro J. M., Harvey C., Trinchieri G.. 1998; Role of interleukin-12 in primary influenza virus infection. J Virol72:4825–4831
    [Google Scholar]
  19. Moran T. M., Isobe H., Fernandez-Sesma A., Schulman J. L.. 1996; Interleukin-4 causes delayed virus clearance in influenza virus-infected mice. J Virol70:5230–5235
    [Google Scholar]
  20. Mori I., Komatsu T., Takeuchi K., Nakakuki K., Sudo M., Kimura Y.. 1995; Viremia induced by influenza virus. Microb Pathog19:237–244
    [Google Scholar]
  21. Oxenius A., Martinic M. M., Hengartner H., Klenerman P.. 1999; CpG-containing oligonucleotides are efficient adjuvants for induction of protective antiviral immune responses with T-cell peptide vaccines. J Virol73:4120–4126
    [Google Scholar]
  22. Pawelec G., Adibzadeh M., Pohla H., Schaudt K.. 1995; Immunosenescence: ageing of the immune system. Immunol Today16:420–422
    [Google Scholar]
  23. Ramshaw I. A., Ramsay A. J., Karupiah G., Rolph M. S., Mahalingam S., Ruby J. C.. 1997; Cytokines and immunity to viral infections. Immunol Rev159:119–135
    [Google Scholar]
  24. Rink L., Cakman I., Kirchner H.. 1998; Altered cytokine production in the elderly. Mech Ageing Dev102:199–209
    [Google Scholar]
  25. Sparwasser T., Koch E. S., Vabulas R. M., Heeg K., Lipford G. B., Ellwart J. W., Wagner H.. 1998; Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol28:2045–2054
    [Google Scholar]
  26. Takeda T., Hosokawa H., Higuchi K.. 1997a; Senescence-accelerated mouse (SAM): a novel murine model of senescence. Exp Gerontol32:105–109
    [Google Scholar]
  27. Takeda T., Matsushita T., Kurozumi M., Takemura K., Higuchi K., Hosokawa M.. 1997b; Pathobiology of the senescence-accelerated mouse (SAM). Exp Gerontol32:117–127
    [Google Scholar]
  28. Yamamoto S., Yamamoto T., Kataoka T., Kuramoto E., Yano O., Tokunaga T.. 1992; Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN and augment IFN-mediated natural killer activity. J Immunol148:4072–4076
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19029-0
Loading
/content/journal/jgv/10.1099/vir.0.19029-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error