Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 Sep;62(9):3723–3730. doi: 10.1128/iai.62.9.3723-3730.1994

Protective effect of rSm28GST-specific T cells in schistosomiasis: role of gamma interferon.

V Pancre 1, I Wolowczuk 1, S Guerret 1, M C Copin 1, A Delanoye 1, A Capron 1, C Auriault 1
PMCID: PMC303023  PMID: 8063386

Abstract

Immunization with a single dose of 50 micrograms of recombinant Schistosoma mansoni 28-kDa glutathione-S-transferase (rSm28GST) was able to induce a reduction in the worm burden, the number of eggs, and the degree of hepatic fibrosis as quantified by the measurement of collagen content in the liver of S. mansoni-infected mice. No relationship was found between anti-Sm28GST immunoglobulin G and immunoglobulin A titers and the levels of protection obtained. Adoptive transfers of Sm28GST-specific total, CD4+, or CD8+ T cells reproduced the protective effect obtained with the recombinant molecule. Moreover, experiments studying in vivo T-cell depletion demonstrated that anti-CD4- or anti-CD8-treated mice showed a significant decrease in the protective effect conferred, suggesting a role of the two T-cell subpopulations in the expression of Sm28GST-mediated protection against hepatic damage. Sm28GST-specific cells produced little interleukin-4 and high levels of gamma interferon. Treatment of immunized mice with anti-gamma interferon antibody totally suppressed the Sm28GST-induced protective effect and led to the rapid death of infected animals, suggesting a role for this cytokine in the expression of the protective immunity obtained after immunization with rSm28GST.

Full text

PDF

Selected References

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

  1. Balloul J. M., Grzych J. M., Pierce R. J., Capron A. A purified 28,000 dalton protein from Schistosoma mansoni adult worms protects rats and mice against experimental schistosomiasis. J Immunol. 1987 May 15;138(10):3448–3453. [PubMed] [Google Scholar]
  2. Boros D. L. Immunopathology of Schistosoma mansoni infection. Clin Microbiol Rev. 1989 Jul;2(3):250–269. doi: 10.1128/cmr.2.3.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boulanger D., Reid G. D., Sturrock R. F., Wolowczuk I., Balloul J. M., Grezel D., Pierce R. J., Otieno M. F., Guerret S., Grimaud J. A. Immunization of mice and baboons with the recombinant Sm28GST affects both worm viability and fecundity after experimental infection with Schistosoma mansoni. Parasite Immunol. 1991 Sep;13(5):473–490. doi: 10.1111/j.1365-3024.1991.tb00545.x. [DOI] [PubMed] [Google Scholar]
  4. Colley D. G. T lymphocytes that contribute to the immunoregulation of granuloma formation in chronic murine schistosomiasis. J Immunol. 1981 Apr;126(4):1465–1468. [PubMed] [Google Scholar]
  5. Courtney M., Buchwalder A., Tessier L. H., Jaye M., Benavente A., Balland A., Kohli V., Lathe R., Tolstoshev P., Lecocq J. P. High-level production of biologically active human alpha 1-antitrypsin in Escherichia coli. Proc Natl Acad Sci U S A. 1984 Feb;81(3):669–673. doi: 10.1073/pnas.81.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Czaja M. J., Weiner F. R., Eghbali M., Giambrone M. A., Eghbali M., Zern M. A. Differential effects of gamma-interferon on collagen and fibronectin gene expression. J Biol Chem. 1987 Sep 25;262(27):13348–13351. [PubMed] [Google Scholar]
  7. Czaja M. J., Weiner F. R., Flanders K. C., Giambrone M. A., Wind R., Biempica L., Zern M. A. In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis. J Cell Biol. 1989 Jun;108(6):2477–2482. doi: 10.1083/jcb.108.6.2477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Czaja M. J., Weiner F. R., Takahashi S., Giambrone M. A., van der Meide P. H., Schellekens H., Biempica L., Zern M. A. Gamma-interferon treatment inhibits collagen deposition in murine schistosomiasis. Hepatology. 1989 Nov;10(5):795–800. doi: 10.1002/hep.1840100508. [DOI] [PubMed] [Google Scholar]
  9. Dunne D. W., Butterworth A. E., Fulford A. J., Kariuki H. C., Langley J. G., Ouma J. H., Capron A., Pierce R. J., Sturrock R. F. Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur J Immunol. 1992 Jun;22(6):1483–1494. doi: 10.1002/eji.1830220622. [DOI] [PubMed] [Google Scholar]
  10. Fidel P. L., Jr, Boros D. L. Regulation of granulomatous inflammation in murine schistosomiasis. IV. Antigen-induced suppressor T cells down-regulate proliferation and IL-2 production. J Immunol. 1990 Aug 15;145(4):1257–1264. [PubMed] [Google Scholar]
  11. Fong T. A., Mosmann T. R. Alloreactive murine CD8+ T cell clones secrete the Th1 pattern of cytokines. J Immunol. 1990 Mar 1;144(5):1744–1752. [PubMed] [Google Scholar]
  12. Gajewski T. F., Fitch F. W. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4245–4252. [PubMed] [Google Scholar]
  13. Grzych J. M., Grezel D., Xu C. B., Neyrinck J. L., Capron M., Ouma J. H., Butterworth A. E., Capron A. IgA antibodies to a protective antigen in human Schistosomiasis mansoni. J Immunol. 1993 Jan 15;150(2):527–535. [PubMed] [Google Scholar]
  14. 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]
  15. James S. L. Activated macrophages as effector cells of protective immunity to schistosomiasis. Immunol Res. 1986;5(2):139–148. doi: 10.1007/BF02917588. [DOI] [PubMed] [Google Scholar]
  16. Lukacs N. W., Boros D. L. Identification of larval cross-reactive and egg-specific antigens involved in granuloma formation in murine schistosomiasis mansoni. Infect Immun. 1991 Sep;59(9):3237–3242. doi: 10.1128/iai.59.9.3237-3242.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. López-De León A., Rojkind M. A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections. J Histochem Cytochem. 1985 Aug;33(8):737–743. doi: 10.1177/33.8.2410480. [DOI] [PubMed] [Google Scholar]
  18. Mathew R. C., Ragheb S., Boros D. L. Recombinant IL-2 therapy reverses diminished granulomatous responsiveness in anti-L3T4-treated, Schistosoma mansoni-infected mice. J Immunol. 1990 Jun 1;144(11):4356–4361. [PubMed] [Google Scholar]
  19. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  20. Murray P. K. Molecular vaccines against animal parasites. Vaccine. 1989 Aug;7(4):291–299. doi: 10.1016/0264-410x(89)90188-6. [DOI] [PubMed] [Google Scholar]
  21. Müller I., Kropf P., Etges R. J., Louis J. A. Gamma interferon response in secondary Leishmania major infection: role of CD8+ T cells. Infect Immun. 1993 Sep;61(9):3730–3738. doi: 10.1128/iai.61.9.3730-3738.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Perrin P. J., Phillips S. M. The molecular basis of granuloma formation in schistosomiasis. I. A T cell-derived suppressor effector factor. J Immunol. 1988 Sep 1;141(5):1714–1719. [PubMed] [Google Scholar]
  24. Phillips S. M., Lammie P. J. Immunopathology of granuloma formation and fibrosis in schistosomiasis. Parasitol Today. 1986 Nov;2(11):296–302. doi: 10.1016/0169-4758(86)90123-7. [DOI] [PubMed] [Google Scholar]
  25. Phillips S. M., Linette G. P., Doughty B. L., Byram J. E., Von Lichtenberg F. In vivo T cell depletion regulates resistance and morbidity in murine schistosomiasis. J Immunol. 1987 Aug 1;139(3):919–926. [PubMed] [Google Scholar]
  26. Pène J., Rousset F., Brière F., Chrétien I., Bonnefoy J. Y., Spits H., Yokota T., Arai N., Arai K., Banchereau J. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6880–6884. doi: 10.1073/pnas.85.18.6880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ragheb S., Boros D. L. Characterization of granuloma T lymphocyte function from Schistosoma mansoni-infected mice. J Immunol. 1989 May 1;142(9):3239–3246. [PubMed] [Google Scholar]
  28. 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]
  29. Smythies L. E., Coulson P. S., Wilson R. A. Monoclonal antibody to IFN-gamma modifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. J Immunol. 1992 Dec 1;149(11):3654–3658. [PubMed] [Google Scholar]
  30. Taylor J. B., Vidal A., Torpier G., Meyer D. J., Roitsch C., Balloul J. M., Southan C., Sondermeyer P., Pemble S., Lecocq J. P. The glutathione transferase activity and tissue distribution of a cloned Mr28K protective antigen of Schistosoma mansoni. EMBO J. 1988 Feb;7(2):465–472. doi: 10.1002/j.1460-2075.1988.tb02834.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Taylor M. G., Bickle Q. D. Irridiated schistosome vaccines. Parasitol Today. 1986 May;2(5):132–134. doi: 10.1016/0169-4758(86)90176-6. [DOI] [PubMed] [Google Scholar]
  32. Wolowczuk I., Auriault C., Gras-Masse H., Vendeville C., Balloul J. M., Tartar A., Capron A. Protective immunity in mice vaccinated with the Schistosoma mansoni P-28-1 antigen. J Immunol. 1989 Feb 15;142(4):1342–1350. [PubMed] [Google Scholar]
  33. Wyler D. J., Ehrlich H. P., Postlethwaite A. E., Raghow R., Murphy M. M. Fibroblast stimulation in schistosomiasis. VII. Egg granulomas secrete factors that stimulate collagen and fibronectin synthesis. J Immunol. 1987 Mar 1;138(5):1581–1586. [PubMed] [Google Scholar]
  34. Xu C. B., Verwaerde C., Grzych J. M., Fontaine J., Capron A. A monoclonal antibody blocking the Schistosoma mansoni 28-kDa glutathione S-transferase activity reduces female worm fecundity and egg viability. Eur J Immunol. 1991 Aug;21(8):1801–1807. doi: 10.1002/eji.1830210804. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES