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. 1993 May;61(5):2162–2171. doi: 10.1128/iai.61.5.2162-2171.1993

Immune response of the female rat genital tract after oral and local immunization with keyhole limpet hemocyanin conjugated to the cholera toxin B subunit.

A C Menge 1, S M Michalek 1, M W Russell 1, J Mestecky 1
PMCID: PMC280817  PMID: 8478106

Abstract

The immune response of the female rat genital tract was evaluated with Lewis rats given primary and secondary immunizations with keyhole limpet hemocyanin (KLH) alone or coupled to the cholera toxin (CT) B subunit (CTB) by the oral or intravaginal-uterine route or a combination of routes. CT (2 to 5 micrograms) was administered as an adjuvant with the KLH-CTB conjugate. While a significant mucosal immunoglobulin A (IgA) response was induced by KLH, there were no significant differences among the immunized groups in the levels of IgA antibodies in salivary gland, gut, vaginal, and uterine secretions, with the exception that rats immunized only orally with the KLH-CTB conjugate lacked a detectable vaginal response. Levels of IgA antibodies to CT, however, were significantly increased in genital tract secretions of rats immunized locally versus orally with the KLH-CTB conjugate. Antibody activity of the IgG isotype against both KLH and CT was significantly elevated in genital tract secretions of rats immunized with KLH-CTB by the oral or intravaginal-uterine route and given genital tract boosters, in comparison with the results for the other groups. IgM antibody titers were generally negligible in the different secretions. An enzyme-linked spot-forming assay revealed IgA and IgG antibody-secreting cells in salivary gland and uterine tissues. A highly significant correlation between the numbers of antibody-secreting cells and antibody titers existed for uterine IgG but not IgA responses to KLH among the different groups of rats. In conclusion, a vigorous local immune response was induced after immunization of the female rat reproductive tract alone or in combination with peroral challenge with the KLH-CTB conjugate.

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Selected References

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  1. Allardyce R., Rademaker M. Female genital tract immunity and infertility after oral vaccination with sperm antigens in mice. Adv Exp Med Biol. 1987;216B:1807–1813. [PubMed] [Google Scholar]
  2. Bergmann K. C., Waldman R. H. Oral immunization with influenza virus: experimental and clinical studies. Curr Top Microbiol Immunol. 1989;146:83–89. doi: 10.1007/978-3-642-74529-4_9. [DOI] [PubMed] [Google Scholar]
  3. Brandtzaeg P. Overview of the mucosal immune system. Curr Top Microbiol Immunol. 1989;146:13–25. doi: 10.1007/978-3-642-74529-4_2. [DOI] [PubMed] [Google Scholar]
  4. Czerkinsky C., Russell M. W., Lycke N., Lindblad M., Holmgren J. Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues. Infect Immun. 1989 Apr;57(4):1072–1077. doi: 10.1128/iai.57.4.1072-1077.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Elson C. O. Cholera toxin and its subunits as potential oral adjuvants. Curr Top Microbiol Immunol. 1989;146:29–33. doi: 10.1007/978-3-642-74529-4_3. [DOI] [PubMed] [Google Scholar]
  6. Elson C. O., Ealding W. Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. J Immunol. 1984 Jun;132(6):2736–2741. [PubMed] [Google Scholar]
  7. Elson C. O., Ealding W., Lefkowitz J. A lavage technique allowing repeated measurement of IgA antibody in mouse intestinal secretions. J Immunol Methods. 1984 Feb 24;67(1):101–108. doi: 10.1016/0022-1759(84)90089-9. [DOI] [PubMed] [Google Scholar]
  8. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry. 1971 Sep;8(9):871–874. doi: 10.1016/0019-2791(71)90454-x. [DOI] [PubMed] [Google Scholar]
  9. Frangakis M. V., Koopman W. J., Kiyono H., Michalek S. M., McGhee J. R. An enzymatic method for preparation of dissociated murine Peyer's patch cells enriched for macrophages. J Immunol Methods. 1982;48(1):33–44. doi: 10.1016/0022-1759(82)90207-1. [DOI] [PubMed] [Google Scholar]
  10. Katz J., Leary R. M., Ward D. C., Harmon C. C., Michalek S. M. Humoral response to Porphyromonas (Bacteroides) gingivalis in rats: time course and T-cell dependence. Infect Immun. 1992 Sep;60(9):3579–3585. doi: 10.1128/iai.60.9.3579-3585.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lande I. J. Systemic immunity developing from intrauterine antigen exposure in the nonpregnant rat. J Reprod Immunol. 1986 Apr;9(1):57–66. doi: 10.1016/0165-0378(86)90025-2. [DOI] [PubMed] [Google Scholar]
  12. Lue C., Prince S. J., Fattom A., Schneerson R., Robbins J. B., Mestecky J. Antibody-secreting peripheral blood lymphocytes induced by immunization with a conjugate consisting of Streptococcus pneumoniae type 12F polysaccharide and diphtheria toxoid. Infect Immun. 1990 Aug;58(8):2547–2554. doi: 10.1128/iai.58.8.2547-2554.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lycke N., Holmgren J. Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens. Immunology. 1986 Oct;59(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  14. McDermott M. R., Bienenstock J. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol. 1979 May;122(5):1892–1898. [PubMed] [Google Scholar]
  15. Mestecky J. The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol. 1987 Jul;7(4):265–276. doi: 10.1007/BF00915547. [DOI] [PubMed] [Google Scholar]
  16. Ogra P. L., Okamoto Y., Freihorst J., LaScolea L. J., Jr, Merrick J. M. Immunization of the gastrointestinal tract with bacterial and viral antigens: implications in mucosal immunity. Immunol Invest. 1989 Jan-May;18(1-4):559–570. doi: 10.3109/08820138909112263. [DOI] [PubMed] [Google Scholar]
  17. Osteen K. G., Hill G. A., Hargrove J. T., Gorstein F. Development of a method to isolate and culture highly purified populations of stromal and epithelial cells from human endometrial biopsy specimens. Fertil Steril. 1989 Dec;52(6):965–972. doi: 10.1016/s0015-0282(16)53160-4. [DOI] [PubMed] [Google Scholar]
  18. Parr E. L., Parr M. B. A comparison of antibody titres in mouse uterine fluid after immunization by several routes, and the effect of the uterus on antibody titres in vaginal fluid. J Reprod Fertil. 1990 Jul;89(2):619–625. doi: 10.1530/jrf.0.0890619. [DOI] [PubMed] [Google Scholar]
  19. Parr E. L., Parr M. B., Thapar M. A comparison of specific antibody responses in mouse vaginal fluid after immunization by several routes. J Reprod Immunol. 1988 Nov;14(2):165–176. doi: 10.1016/0165-0378(88)90067-8. [DOI] [PubMed] [Google Scholar]
  20. Pierce N. F., Cray W. C., Jr Cellular dissemination of priming for a mucosal immune response to cholera toxin in rats. J Immunol. 1981 Dec;127(6):2461–2464. [PubMed] [Google Scholar]
  21. Renegar K. B., Small P. A., Jr Passive transfer of local immunity to influenza virus infection by IgA antibody. J Immunol. 1991 Mar 15;146(6):1972–1978. [PubMed] [Google Scholar]
  22. Russell M. W., Wu H. Y. Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II of Streptococcus mutans coupled to the cholera toxin B subunit. Infect Immun. 1991 Nov;59(11):4061–4070. doi: 10.1128/iai.59.11.4061-4070.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Steele M. G., Wira C. R. IgA in uterine tissue: effect of estrous cycle, hormone treatment and intrauterine immunization. J Steroid Biochem. 1989;34(1-6):229–234. doi: 10.1016/0022-4731(89)90086-1. [DOI] [PubMed] [Google Scholar]
  24. Thapar M. A., Parr E. L., Parr M. B. The effect of adjuvants on antibody titers in mouse vaginal fluid after intravaginal immunization. J Reprod Immunol. 1990 Jun;17(3):207–216. doi: 10.1016/0165-0378(90)90003-o. [DOI] [PubMed] [Google Scholar]
  25. Wilson A. D., Clarke C. J., Stokes C. R. Whole cholera toxin and B subunit act synergistically as an adjuvant for the mucosal immune response of mice to keyhole limpet haemocyanin. Scand J Immunol. 1990 Apr;31(4):443–451. doi: 10.1111/j.1365-3083.1990.tb02791.x. [DOI] [PubMed] [Google Scholar]
  26. Wira C. R., Sandoe C. P. Effect of uterine immunization and oestradiol on specific IgA and IgG antibodies in uterine, vaginal and salivary secretions. Immunology. 1989 Sep;68(1):24–30. [PMC free article] [PubMed] [Google Scholar]
  27. Wu H. Y., Russell M. W. Induction of mucosal immunity by intranasal application of a streptococcal surface protein antigen with the cholera toxin B subunit. Infect Immun. 1993 Jan;61(1):314–322. doi: 10.1128/iai.61.1.314-322.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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