Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1997 Nov;92(3):328–333. doi: 10.1046/j.1365-2567.1997.00356.x

Mucosal tolerance is associated with, but independent of, up-regulation Th2 responses.

D A Wolvers 1, M J van der Cammen 1, G Kraal 1
PMCID: PMC1363792  PMID: 9486104

Abstract

Intranasal administration of protein antigen is an efficient way to induce mucosal tolerance. Suppressive mechanisms that might be involved in this phenomenon include down-regulation of T-helper type-1 (Th1)-mediated processes by Th2 cells. However, since Th2 responses can also be subjected to mucosal tolerance, we wanted to investigate whether suppression of a typical Th1 response, such as a delayed-type hypersensitivity (DTH) reaction by intranasal tolerance induction, was causally related to up-regulation of Th2 responses. We therefore treated mice either systemically or locally with anti-interleukin-4 (IL-4) or anti-IL-10 antibodies before intranasal tolerance induction or before sensitization for DTH to see whether we could prevent or abrogate tolerance. Although the up-regulation of antigen-specific IgE levels in tolerant mice could be prevented by anti-IL-4 treatment, the extent of tolerance as measured by suppression of DTH was not affected. We therefore conclude that up-regulation of Th2 responses observed after intranasal tolerance induction is an additional or consequential rather than a necessary reaction.

Full text

PDF
328

Selected References

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

  1. Abrams J. S., Roncarolo M. G., Yssel H., Andersson U., Gleich G. J., Silver J. E. Strategies of anti-cytokine monoclonal antibody development: immunoassay of IL-10 and IL-5 in clinical samples. Immunol Rev. 1992 Jun;127:5–24. doi: 10.1111/j.1600-065x.1992.tb01406.x. [DOI] [PubMed] [Google Scholar]
  2. Aroeira L. S., Cardillo F., De Albuquerque D. A., Vaz N. M., Mengel J. Anti-IL-10 treatment does not block either the induction or the maintenance of orally induced tolerance to OVA. Scand J Immunol. 1995 Apr;41(4):319–323. doi: 10.1111/j.1365-3083.1995.tb03573.x. [DOI] [PubMed] [Google Scholar]
  3. Chatelain R., Varkila K., Coffman R. L. IL-4 induces a Th2 response in Leishmania major-infected mice. J Immunol. 1992 Feb 15;148(4):1182–1187. [PubMed] [Google Scholar]
  4. Chen Y., Inobe J., Marks R., Gonnella P., Kuchroo V. K., Weiner H. L. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature. 1995 Jul 13;376(6536):177–180. doi: 10.1038/376177a0. [DOI] [PubMed] [Google Scholar]
  5. Chen Y., Kuchroo V. K., Inobe J., Hafler D. A., Weiner H. L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science. 1994 Aug 26;265(5176):1237–1240. doi: 10.1126/science.7520605. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Finkelman F. D., Lees A., Birnbaum R., Gause W. C., Morris S. C. Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J Immunol. 1996 Aug 15;157(4):1406–1414. [PubMed] [Google Scholar]
  8. Friedman A., Weiner H. L. Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6688–6692. doi: 10.1073/pnas.91.14.6688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fujihashi K., Yamamoto M., McGhee J. R., Kiyono H. alpha beta T cell receptor-positive intraepithelial lymphocytes with CD4+, CD8- and CD4+, CD8+ phenotypes from orally immunized mice provide Th2-like function for B cell responses. J Immunol. 1993 Dec 15;151(12):6681–6691. [PubMed] [Google Scholar]
  10. Garside P., Steel M., Worthey E. A., Satoskar A., Alexander J., Bluethmann H., Liew F. Y., Mowat A. M. T helper 2 cells are subject to high dose oral tolerance and are not essential for its induction. J Immunol. 1995 Jun 1;154(11):5649–5655. [PubMed] [Google Scholar]
  11. Hoyne G. F., Askonas B. A., Hetzel C., Thomas W. R., Lamb J. R. Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo. Int Immunol. 1996 Mar;8(3):335–342. doi: 10.1093/intimm/8.3.335. [DOI] [PubMed] [Google Scholar]
  12. Ibrahim M. A., Chain B. M., Katz D. R. The injured cell: the role of the dendritic cell system as a sentinel receptor pathway. Immunol Today. 1995 Apr;16(4):181–186. doi: 10.1016/0167-5699(95)80118-9. [DOI] [PubMed] [Google Scholar]
  13. Kuchroo V. K., Das M. P., Brown J. A., Ranger A. M., Zamvil S. S., Sobel R. A., Weiner H. L., Nabavi N., Glimcher L. H. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell. 1995 Mar 10;80(5):707–718. doi: 10.1016/0092-8674(95)90349-6. [DOI] [PubMed] [Google Scholar]
  14. Kühn R., Rajewsky K., Müller W. Generation and analysis of interleukin-4 deficient mice. Science. 1991 Nov 1;254(5032):707–710. doi: 10.1126/science.1948049. [DOI] [PubMed] [Google Scholar]
  15. Lider O., Santos L. M., Lee C. S., Higgins P. J., Weiner H. L. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. II. Suppression of disease and in vitro immune responses is mediated by antigen-specific CD8+ T lymphocytes. J Immunol. 1989 Feb 1;142(3):748–752. [PubMed] [Google Scholar]
  16. McMenamin C., Oliver J., Girn B., Holt B. J., Kees U. R., Thomas W. R., Holt P. G. Regulation of T-cell sensitization at epithelial surfaces in the respiratory tract: suppression of IgE responses to inhaled antigens by CD3+ Tcr alpha-/beta- lymphocytes (putative gamma/delta T cells). Immunology. 1991 Oct;74(2):234–239. [PMC free article] [PubMed] [Google Scholar]
  17. McMenamin C., Pimm C., McKersey M., Holt P. G. Regulation of IgE responses to inhaled antigen in mice by antigen-specific gamma delta T cells. Science. 1994 Sep 23;265(5180):1869–1871. doi: 10.1126/science.7916481. [DOI] [PubMed] [Google Scholar]
  18. Melamed D., Friedman A. Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin. Eur J Immunol. 1993 Apr;23(4):935–942. doi: 10.1002/eji.1830230426. [DOI] [PubMed] [Google Scholar]
  19. Miller A., Lider O., Roberts A. B., Sporn M. B., Weiner H. L. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):421–425. doi: 10.1073/pnas.89.1.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mosmann T. R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138–146. doi: 10.1016/0167-5699(96)80606-2. [DOI] [PubMed] [Google Scholar]
  21. Ohara J., Paul W. E. Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature. 1985 May 23;315(6017):333–336. doi: 10.1038/315333a0. [DOI] [PubMed] [Google Scholar]
  22. Sander B., Höidén I., Andersson U., Möller E., Abrams J. S. Similar frequencies and kinetics of cytokine producing cells in murine peripheral blood and spleen. Cytokine detection by immunoassay and intracellular immunostaining. J Immunol Methods. 1993 Dec 3;166(2):201–214. doi: 10.1016/0022-1759(93)90361-a. [DOI] [PubMed] [Google Scholar]
  23. Tian J., Atkinson M. A., Clare-Salzler M., Herschenfeld A., Forsthuber T., Lehmann P. V., Kaufman D. L. Nasal administration of glutamate decarboxylase (GAD65) peptides induces Th2 responses and prevents murine insulin-dependent diabetes. J Exp Med. 1996 Apr 1;183(4):1561–1567. doi: 10.1084/jem.183.4.1561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tilney N. L. Patterns of lymphatic drainage in the adult laboratory rat. J Anat. 1971 Sep;109(Pt 3):369–383. [PMC free article] [PubMed] [Google Scholar]
  25. Whitacre C. C., Gienapp I. E., Orosz C. G., Bitar D. M. Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. J Immunol. 1991 Oct 1;147(7):2155–2163. [PubMed] [Google Scholar]
  26. van Halteren A. G., van der Cammen M. J., Biewenga J., Savelkoul H. F., Kraal G. IgE and mast cell response on intestinal allergen exposure: a murine model to study the onset of food allergy. J Allergy Clin Immunol. 1997 Jan;99(1 Pt 1):94–99. doi: 10.1016/s0091-6749(97)70305-1. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES