Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Jan 1;173(1):159–166. doi: 10.1084/jem.173.1.159

Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni

PMCID: PMC2118762  PMID: 1824635

Abstract

In the mouse, infection with Schistosoma mansoni results in an egg- producing infection and associated disease, whereas vaccination with attenuated larval stages produces a substantial and specific immunity in the absence of egg-induced pathology. Preliminary data showing enhanced interleukin-5 (IL-5) production by T cells from infected mice and interferon gamma (IFN-gamma) synthesis by cells from vaccinated animals (7), suggested differential CD4+ subset stimulation by the different parasite stimuli. To confirm this hypothesis, lymphocytes from vaccinated or infected animals were compared for their ability to produce IFN-gamma and IL-2 (secreted by Th1 cells) as compared with IL- 4 and IL-5 (characteristic Th2 cytokines). After stimulation with specific antigen or mitogen, T cells from vaccinated mice or prepatently infected animals responded primarily with Th1 lymphokines, whereas lymphocytes from patently infected mice instead produced Th2 cytokines. The Th2 response in infected animals was shown to be induced by schistosome eggs and directed largely against egg antigens, whereas the Th1 reactivity in vaccinated mice was triggered primarily by larval antigens. Interestingly, Th1 responses in mice carrying egg-producing infections were found to be profoundly downregulated. Moreover, the injection of eggs into vaccinated mice resulted in a reduction of antigen and mitogen-stimulated Th1 function accompanied by a coincident expression of Th2 responses. Together, the data suggest that coincident with the induction of Th2 responses, murine schistosome infection results in an inhibition of potentially protective Th1 function. This previously unrecognized downregulation of Th1 cytokine production may be an important immunological consequence of helminth infection related to host adaptation.

Full Text

The Full Text of this article is available as a PDF (956.3 KB).

Selected References

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

  1. Bickle Q. D., Andrews B. J. Resistance following drug attenuation (Ro 11-3128 or oxamniquine) of early Schistosoma mansoni infections in mice. Parasitology. 1985 Apr;90(Pt 2):325–338. doi: 10.1017/s0031182000051027. [DOI] [PubMed] [Google Scholar]
  2. Boctor F. N., Nash T. E., Cheever A. W. Isolation of a polysaccharide antigen from Schistosoma mansoni eggs. J Immunol. 1979 Jan;122(1):39–43. [PubMed] [Google Scholar]
  3. Boros D. L., Warren K. S. Delayed hypersensitivity-type granuloma formation and dermal reaction induced and elicited by a soluble factor isolated from Schistosoma mansoni eggs. J Exp Med. 1970 Sep 1;132(3):488–507. doi: 10.1084/jem.132.3.488. [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. Coffman R. L., Seymour B. W., Hudak S., Jackson J., Rennick D. Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice. Science. 1989 Jul 21;245(4915):308–310. doi: 10.1126/science.2787531. [DOI] [PubMed] [Google Scholar]
  6. Colley D. G., Colley M. D. Protective immunity and vaccines to schistosomiasis. Parasitol Today. 1989 Nov;5(11):350–355. doi: 10.1016/0169-4758(89)90106-3. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Czerkinsky C., Andersson G., Ekre H. P., Nilsson L. A., Klareskog L., Ouchterlony O. Reverse ELISPOT assay for clonal analysis of cytokine production. I. Enumeration of gamma-interferon-secreting cells. J Immunol Methods. 1988 May 25;110(1):29–36. doi: 10.1016/0022-1759(88)90079-8. [DOI] [PubMed] [Google Scholar]
  10. Dean D. A. Schistosoma and related genera: acquired resistance in mice. Exp Parasitol. 1983 Feb;55(1):1–104. doi: 10.1016/0014-4894(83)90002-4. [DOI] [PubMed] [Google Scholar]
  11. Espevik T., Figari I. S., Shalaby M. R., Lackides G. A., Lewis G. D., Shepard H. M., Palladino M. A., Jr Inhibition of cytokine production by cyclosporin A and transforming growth factor beta. J Exp Med. 1987 Aug 1;166(2):571–576. doi: 10.1084/jem.166.2.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Finkelman F. D., Holmes J., Katona I. M., Urban J. F., Jr, Beckmann M. P., Park L. S., Schooley K. A., Coffman R. L., Mosmann T. R., Paul W. E. Lymphokine control of in vivo immunoglobulin isotype selection. Annu Rev Immunol. 1990;8:303–333. doi: 10.1146/annurev.iy.08.040190.001511. [DOI] [PubMed] [Google Scholar]
  13. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Freedman D. O., Ottesen E. A. Eggs of Schistosoma mansoni stimulate endothelial cell proliferation in vitro. J Infect Dis. 1988 Sep;158(3):556–562. doi: 10.1093/infdis/158.3.556. [DOI] [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. James S. L., Pearce E. J., Sher A. Induction of protective immunity against Schistosoma mansoni by a non living vaccine. I. Partial characterization of antigens recognized by antibodies from mice immunized with soluble schistosome extracts. J Immunol. 1985 May;134(5):3432–3438. [PubMed] [Google Scholar]
  17. James S. L., Sher A. Cell-mediated immune response to schistosomiasis. Curr Top Microbiol Immunol. 1990;155:21–31. doi: 10.1007/978-3-642-74983-4_2. [DOI] [PubMed] [Google Scholar]
  18. McHugh S. M., Coulson P. S., Wilson R. A. The relationship between pathology and resistance to reinfection with Schistosoma mansoni in mice: a causal mechanism of resistance in chronic infections. Parasitology. 1987 Feb;94(Pt 1):81–91. doi: 10.1017/s0031182000053476. [DOI] [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. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  21. Mosmann T. R., Fong T. A. Specific assays for cytokine production by T cells. J Immunol Methods. 1989 Jan 17;116(2):151–158. doi: 10.1016/0022-1759(89)90198-1. [DOI] [PubMed] [Google Scholar]
  22. Schumacher J. H., O'Garra A., Shrader B., van Kimmenade A., Bond M. W., Mosmann T. R., Coffman R. L. The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol. 1988 Sep 1;141(5):1576–1581. [PubMed] [Google Scholar]
  23. Scott P., Natovitz P., Coffman R. L., Pearce E., Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. doi: 10.1084/jem.168.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scott P., Pearce E., Cheever A. W., Coffman R. L., Sher A. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol Rev. 1989 Dec;112:161–182. doi: 10.1111/j.1600-065x.1989.tb00557.x. [DOI] [PubMed] [Google Scholar]
  25. Sher A., Coffman R. L., Hieny S., Scott P., Cheever A. W. Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni. Proc Natl Acad Sci U S A. 1990 Jan;87(1):61–65. doi: 10.1073/pnas.87.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smithers S. R., Terry R. J. The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology. 1965 Nov;55(4):695–700. doi: 10.1017/s0031182000086248. [DOI] [PubMed] [Google Scholar]
  27. Vignali D. A., Crocker P., Bickle Q. D., Cobbold S., Waldmann H., Taylor M. G. A role for CD4+ but not CD8+ T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-3128-terminated infections. Immunology. 1989 Aug;67(4):466–472. [PMC free article] [PubMed] [Google Scholar]
  28. Wilson R. A., Coulson P. S., McHugh S. M. A significant part of the 'concomitant immunity' of mice to Schistosoma mansoni is the consequence of a leaky hepatic portal system, not immune killing. Parasite Immunol. 1983 Nov;5(6):595–601. doi: 10.1111/j.1365-3024.1983.tb00776.x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES