Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1997 Feb;90(2):161–164. doi: 10.1046/j.1365-2567.1997.00191.x

Suppression of murine collagen-induced arthritis by nasal administration of collagen.

L K Myers 1, J M Seyer 1, J M Stuart 1, A H Kang 1
PMCID: PMC1456748  PMID: 9135541

Abstract

DBA/1 mice were administered type II collagen (CII) or collagen peptides intranasally before systemic immunization to determine whether tolerance could be induced and autoimmune arthritis suppressed. Although prior experiments have demonstrated that collagen given intravenously or orally is effective, the respiratory mucosal route offers several theoretical advantages for dosing peptides, in addition to ease of use. Intact CII, CB11 and a synthetic peptide containing the immunodominant T-cell epitope recognized by H-2q mice were all effective in reducing the incidence and severity of arthritis and the immune response to CII. Since previous studies have demonstrated the importance of IgG2 antibody subclasses to the induction of collagen-induced arthritis, total immunoglobulin G (IgG), IgG1, and IgG2a and IgG2b were measured. IgG2 antibody subclasses were significantly downregulated by the treatment regimen, whereas a slight decrease in IgG1 antibodies was noted that was not significant. In an effort to determine the mechanism by which arthritis was attenuated, cervical lymph node and spleen cells from treated mice were cultured separately with CII and supernatants tested for the presence of T-cell lymphokines. The cells provided a T-helper 2 (Th2)-like response to CII, with T cells from lymph nodes secreting interleukin-4 (IL-4) and splenocytes secreting both IL-4 and IL-10, whereas a Th1-like response was detected in immunized mice not tolerized with CII. These findings indicate that the downregulation of arthritis that occurs with intranasal administration of CII is associated with Th2-type lymphokine profile and a decrease in complement-fixing antibody subclass.

Full text

PDF
161

Selected References

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

  1. Brand D. D., Myers L. K., Terato K., Whittington K. B., Stuart J. M., Kang A. H., Rosloniec E. F. Characterization of the T cell determinants in the induction of autoimmune arthritis by bovine alpha 1(II)-CB11 in H-2q mice. J Immunol. 1994 Mar 15;152(6):3088–3097. [PubMed] [Google Scholar]
  2. Cibotti R., Kanellopoulos J. M., Cabaniols J. P., Halle-Panenko O., Kosmatopoulos K., Sercarz E., Kourilsky P. Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):416–420. doi: 10.1073/pnas.89.1.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cremer M. A., Hernandez A. D., Townes A. S., Stuart J. M., Kang A. H. Collagen-induced arthritis in rats: antigen-specific suppression of arthritis and immunity by intravenously injected native type II collagen. J Immunol. 1983 Dec;131(6):2995–3000. [PubMed] [Google Scholar]
  4. Dick A. D., Cheng Y. F., Liversidge J., Forrester J. V. Intranasal administration of retinal antigens suppresses retinal antigen-induced experimental autoimmune uveoretinitis. Immunology. 1994 Aug;82(4):625–631. [PMC free article] [PubMed] [Google Scholar]
  5. Gammon G., Sercarz E. E., Benichou G. The dominant self and the cryptic self: shaping the autoreactive T-cell repertoire. Immunol Today. 1991 Jun;12(6):193–195. doi: 10.1016/0167-5699(91)90052-U. [DOI] [PubMed] [Google Scholar]
  6. Kourilsky P., Jaulin C., Ley V. The structure and function of MHC molecules. Possible implications for the control of tumor growth by MHC-restricted T cells. Semin Cancer Biol. 1991 Oct;2(5):275–282. [PubMed] [Google Scholar]
  7. Ma C. G., Zhang G. X., Xiao B. G., Wang Z. Y., Link J., Olsson T., Link H. Mucosal tolerance to experimental autoimmune myasthenia gravis is associated with down-regulation of AChR-specific IFN-gamma-expressing Th1-like cells and up-regulation of TGF-beta mRNA in mononuclear cells. Ann N Y Acad Sci. 1996 Feb 13;778:273–287. doi: 10.1111/j.1749-6632.1996.tb21135.x. [DOI] [PubMed] [Google Scholar]
  8. Myers L. K., Stuart J. M., Kang A. H. A CD4 cell is capable of transferring suppression of collagen-induced arthritis. J Immunol. 1989 Dec 15;143(12):3976–3980. [PubMed] [Google Scholar]
  9. Myers L. K., Stuart J. M., Seyer J. M., Kang A. H. Identification of an immunosuppressive epitope of type II collagen that confers protection against collagen-induced arthritis. J Exp Med. 1989 Dec 1;170(6):1999–2010. doi: 10.1084/jem.170.6.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Myers L. K., Terato K., Seyer J. M., Stuart J. M., Kang A. H. Characterization of a tolerogenic T cell epitope of type II collagen and its relevance to collagen-induced arthritis. J Immunol. 1992 Aug 15;149(4):1439–1443. [PubMed] [Google Scholar]
  11. Nagler-Anderson C., Bober L. A., Robinson M. E., Siskind G. W., Thorbecke G. J. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7443–7446. doi: 10.1073/pnas.83.19.7443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Staines N. A., Harper N., Ward F. J., Malmström V., Holmdahl R., Bansal S. Mucosal tolerance and suppression of collagen-induced arthritis (CIA) induced by nasal inhalation of synthetic peptide 184-198 of bovine type II collagen (CII) expressing a dominant T cell epitope. Clin Exp Immunol. 1996 Mar;103(3):368–375. doi: 10.1111/j.1365-2249.1996.tb08289.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Thompson H. S., Staines N. A. Gastric administration of type II collagen delays the onset and severity of collagen-induced arthritis in rats. Clin Exp Immunol. 1986 Jun;64(3):581–586. [PMC free article] [PubMed] [Google Scholar]
  14. Trentham D. E., Townes A. S., Kang A. H. Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977 Sep 1;146(3):857–868. doi: 10.1084/jem.146.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wooley P. H., Luthra H. S., Stuart J. M., David C. S. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. doi: 10.1084/jem.154.3.688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wraith D. C. Antigen-specific immunotherapy of autoimmune disease: a commentary. Clin Exp Immunol. 1996 Mar;103(3):349–352. doi: 10.1111/j.1365-2249.1996.tb08286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES