Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Feb 1;90(3):948–952. doi: 10.1073/pnas.90.3.948

Helminth infection results in decreased virus-specific CD8+ cytotoxic T-cell and Th1 cytokine responses as well as delayed virus clearance.

J K Actor 1, M Shirai 1, M C Kullberg 1, R M Buller 1, A Sher 1, J A Berzofsky 1
PMCID: PMC45787  PMID: 8094248

Abstract

During the time of egg deposition, schistosome-infected mice exhibit a downregulation in interleukin 2 and interferon gamma production toward parasite antigens, mitogens, and foreign nonparasite protein antigens. To determine whether this imbalance in cytokine response would impact on CD8+ cytotoxic T-lymphocyte (CTL) responses, as well as on immune clearance of viral infections, we challenged Schistosoma mansoni-infected BALB/c mice, when cytokine imbalance was prominent, with a recombinant vaccinia virus expressing human immunodeficiency virus type 1 gp160. In contrast to control vaccinia-infected animals, S. mansoni plus vaccinia-infected mice did not produce significant Th1 cytokine responses upon in vitro stimulation with recombinant gp120, consistent with previous results for nonparasite antigens. However, more striking was the downregulation of the virus-specific CTL response not previously studied. Spleen cells from vaccinia-infected control mice displayed strong CD8+ cytolytic activity against gp160-transfected fibroblasts and fibroblasts pulsed with a peptide (P18) representing a CTL epitope of gp160. In contrast, mice coinfected with S. mansoni and vaccinia manifested absent or markedly reduced in vitro CTL activity even in the presence of exogenous interleukin 2. To determine whether this immune dysregulation might impact on viral clearance, we measured virus titers in tissues as a function of time. Mice infected with vaccinia virus alone rapidly cleared the virus, whereas in animals coinfected with S. mansoni, viral clearance was delayed by as much as 3 weeks in the liver and by several days in the spleen and lungs. These observations suggest that helminth infection may influence immune responses to concurrent viral infections.

Full text

PDF
948

Images in this article

949Image
on p.949

Selected References

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

  1. Bassily S., Dunn M. A., Farid Z., Kilpatrick M. E., El-Masry N. A., Kamel I. A., El Alamy M., Murphy B. L. Chronic hepatitis B in patients with schistosomiasis mansoni. J Trop Med Hyg. 1983 Apr;86(2):67–71. [PubMed] [Google Scholar]
  2. Blattner W. A. HIV epidemiology: past, present, and future. FASEB J. 1991 Jul;5(10):2340–2348. doi: 10.1096/fasebj.5.10.2065886. [DOI] [PubMed] [Google Scholar]
  3. Buller R. M., Wallace G. D. Reexamination of the efficacy of vaccination against mousepox. Lab Anim Sci. 1985 Oct;35(5):473–476. [PubMed] [Google Scholar]
  4. Chakrabarti S., Robert-Guroff M., Wong-Staal F., Gallo R. C., Moss B. Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature. 1986 Apr 10;320(6062):535–537. doi: 10.1038/320535a0. [DOI] [PubMed] [Google Scholar]
  5. Curry R. C., Kiener P. A., Spitalny G. L. A sensitive immunochemical assay for biologically active MuIFN-gamma. J Immunol Methods. 1987 Nov 23;104(1-2):137–142. doi: 10.1016/0022-1759(87)90497-2. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Earl P. L., Koenig S., Moss B. Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses. J Virol. 1991 Jan;65(1):31–41. doi: 10.1128/jvi.65.1.31-41.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eltoum I. A., Ghalib H. W., Abdel Gadir A. F., Suliaman S. M., Homeida M. M. Lack of association between schistosomiasis and hepatitis B virus infection in Gezira-Managil area, Sudan. Trans R Soc Trop Med Hyg. 1991 Jan-Feb;85(1):81–82. doi: 10.1016/0035-9203(91)90168-x. [DOI] [PubMed] [Google Scholar]
  9. Finkelman F. D., Pearce E. J., Urban J. F., Jr, Sher A. Regulation and biological function of helminth-induced cytokine responses. Immunol Today. 1991 Mar;12(3):A62–A66. doi: 10.1016/S0167-5699(05)80018-0. [DOI] [PubMed] [Google Scholar]
  10. Grzych J. M., Pearce E., Cheever A., Caulada Z. A., Caspar P., Heiny S., Lewis F., Sher A. Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol. 1991 Feb 15;146(4):1322–1327. [PubMed] [Google Scholar]
  11. Hu-Li J., Ohara J., Watson C., Tsang W., Paul W. E. Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT.4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S). J Immunol. 1989 Feb 1;142(3):800–807. [PubMed] [Google Scholar]
  12. Hyams K. C., el Alamy M. A., Pazzaglia G., el Ghorab N. M., Sidhom O., Habib M., Dunn M. A. Risk of hepatitis B infection among Egyptians infected with Schistosoma mansoni. Am J Trop Med Hyg. 1986 Sep;35(5):1035–1039. doi: 10.4269/ajtmh.1986.35.1035. [DOI] [PubMed] [Google Scholar]
  13. Jarrett E., Bazin H. Elevation of total serum IgE in rats following helminth parasite infection. Nature. 1974 Oct 18;251(5476):613–614. doi: 10.1038/251613a0. [DOI] [PubMed] [Google Scholar]
  14. Kullberg M. C., Pearce E. J., Hieny S. E., Sher A., Berzofsky J. A. Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen. J Immunol. 1992 May 15;148(10):3264–3270. [PubMed] [Google Scholar]
  15. Madwar M. A., el Tahawy M., Strickland G. T. The relationship between uncomplicated schistosomiasis and hepatitis B infection. Trans R Soc Trop Med Hyg. 1989 Mar-Apr;83(2):233–236. doi: 10.1016/0035-9203(89)90657-3. [DOI] [PubMed] [Google Scholar]
  16. Nabholz M., MacDonald H. R. Cytolytic T lymphocytes. Annu Rev Immunol. 1983;1:273–306. doi: 10.1146/annurev.iy.01.040183.001421. [DOI] [PubMed] [Google Scholar]
  17. Pearce E. J., Caspar P., Grzych J. M., Lewis F. A., Sher A. Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med. 1991 Jan 1;173(1):159–166. doi: 10.1084/jem.173.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ruby J., Ramshaw I. The antiviral activity of immune CD8+ T cells is dependent on interferon-gamma. Lymphokine Cytokine Res. 1991 Oct;10(5):353–358. [PubMed] [Google Scholar]
  19. Sher A., Fiorentino D., Caspar P., Pearce E., Mosmann T. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991 Oct 15;147(8):2713–2716. [PubMed] [Google Scholar]
  20. Shirai M., Pendleton C. D., Berzofsky J. A. Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules. J Immunol. 1992 Mar 15;148(6):1657–1667. [PubMed] [Google Scholar]
  21. Sprent J., Schaefer M., Lo D., Korngold R. Functions of purified L3T4+ and Lyt-2+ cells in vitro and in vivo. Immunol Rev. 1986 Jun;91:195–218. doi: 10.1111/j.1600-065x.1986.tb01489.x. [DOI] [PubMed] [Google Scholar]
  22. Takahashi H., Cohen J., Hosmalin A., Cease K. B., Houghten R., Cornette J. L., DeLisi C., Moss B., Germain R. N., Berzofsky J. A. An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1988 May;85(9):3105–3109. doi: 10.1073/pnas.85.9.3105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsubota H., Lord C. I., Watkins D. I., Morimoto C., Letvin N. L. A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. J Exp Med. 1989 Apr 1;169(4):1421–1434. doi: 10.1084/jem.169.4.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  25. Warren K. S., Rosenthal M. S., Domingo E. O. Mouse hepatitis virus (MHV3) infection in chronic murine schistosomiasis mansoni. Bull N Y Acad Med. 1969 Feb;45(2):211–224. [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES