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. 1994 Aug;62(8):3528–3535. doi: 10.1128/iai.62.8.3528-3535.1994

An in vitro model for immune control of chlamydial growth in polarized epithelial cells.

J U Igietseme 1, P B Wyrick 1, D Goyeau 1, R G Rank 1
PMCID: PMC302987  PMID: 8039923

Abstract

A polarized epithelial culture system and chlamydia-specific T-cell lines and clones were employed to investigate the ability and mechanisms by which T cells control the growth of chlamydiae in epithelial cells. Monolayers of polarized mouse epithelial cells were infected with the Chlamydia trachomatis agent of mouse pneumonitis (MoPn) and then exposed to antigen-stimulated MoPn-specific T-cell lines and clones. The results revealed that in vivo-protective MoPn-specific T-cell lines and clone 2.14-0 were capable of inhibiting the growth of MoPn in polarized epithelial cells. In contrast, the nonprotective MoPn-specific T-cell clone 2.14-3, naive splenic T cells, and a control T-cell clone could not inhibit the growth of MoPn in epithelial cells. Transmission electron microscopic analysis of infected epithelial cells which were exposed to clone 2.14-0 confirmed the absence of an established infection, as deduced from the virtual absence of inclusions in the cells. Antigen-specific activation of clone 2.14-0 was required for the MoPn-inhibitory function, since the absence of antigenic stimulation or stimulation with a heterologous chlamydial agent did not result in MoPn growth inhibition. Activation of clone 2.14-0 resulted in acquisition of the capacity to inhibit growth of both homologous (MoPn) and heterologous chlamydial agents. Close interaction between epithelial cells and clone 2.14-0 was required for the MoPn-inhibitory action, because separation of the cell types by a filter with a pore size of 0.45, 3.0, or even 8.0 microns abrogated MoPn inhibition. Protective T cells may act at close range in the epithelium to control chlamydial growth, possibly involving short-range-acting cytokines. The ability of antigen-stimulated T-cell lines and clones to inhibit chlamydial growth in polarized epithelial cultures could be a useful method for identifying protective T-cell clones and antigenic peptide fragments containing protective epitopes.

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Selected References

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  1. Allen J. E., Locksley R. M., Stephens R. S. A single peptide from the major outer membrane protein of Chlamydia trachomatis elicits T cell help for the production of antibodies to protective determinants. J Immunol. 1991 Jul 15;147(2):674–679. [PubMed] [Google Scholar]
  2. 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]
  3. Brandtzaeg P., Sollid L. M., Thrane P. S., Kvale D., Bjerke K., Scott H., Kett K., Rognum T. O. Lymphoepithelial interactions in the mucosal immune system. Gut. 1988 Aug;29(8):1116–1130. doi: 10.1136/gut.29.8.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ferguson A., Parrott D. M. The effect of antigen deprivation on thymus-dependent and thymus-independent lymphocytes in the small intestine of the mouse. Clin Exp Immunol. 1972 Dec;12(4):477–488. [PMC free article] [PubMed] [Google Scholar]
  5. Fraser C. E., McComb D. E., Murray E. S., MacDonald A. B. Immunity to chlamydial infections of the eye. IV. Immunity in owl monkeys to reinfection with trachoma. Arch Ophthalmol. 1975 Jul;93(7):518–521. doi: 10.1001/archopht.1975.01010020534010. [DOI] [PubMed] [Google Scholar]
  6. Grayston J. T., Wang S. P., Yeh L. J., Kuo C. C. Importance of reinfection in the pathogenesis of trachoma. Rev Infect Dis. 1985 Nov-Dec;7(6):717–725. doi: 10.1093/clinids/7.6.717. [DOI] [PubMed] [Google Scholar]
  7. Igietseme J. U., Ramsey K. H., Magee D. M., Williams D. M., Kincy T. J., Rank R. G. Resolution of murine chlamydial genital infection by the adoptive transfer of a biovar-specific, Th1 lymphocyte clone. Reg Immunol. 1993 Nov-Dec;5(6):317–324. [PubMed] [Google Scholar]
  8. Igietseme J. U., Rank R. G. Susceptibility to reinfection after a primary chlamydial genital infection is associated with a decrease of antigen-specific T cells in the genital tract. Infect Immun. 1991 Apr;59(4):1346–1351. doi: 10.1128/iai.59.4.1346-1351.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson A. P., Osborn M. F., Thomas B. J., Hetherington C. M., Taylor-Robinson D. Immunity to reinfection of the genital tract of marmosets with Chlamydia trachomatis. Br J Exp Pathol. 1981 Dec;62(6):606–613. [PMC free article] [PubMed] [Google Scholar]
  10. Katz B. P., Batteiger B. E., Jones R. B. Effect of prior sexually transmitted disease on the isolation of Chlamydia trachomatis. Sex Transm Dis. 1987 Jul-Sep;14(3):160–164. doi: 10.1097/00007435-198707000-00008. [DOI] [PubMed] [Google Scholar]
  11. Lamont H. C., Semine D. Z., Leveille C., Nichols R. L. Immunity to vaginal reinfection in female guinea pigs infected sexually with Chlamydia of guinea pig inclusion conjunctivitis. Infect Immun. 1978 Mar;19(3):807–813. doi: 10.1128/iai.19.3.807-813.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lehner T., Walker P., Bergmeier L. A., Haron J. A. Immunogenicity of synthetic peptides derived from the sequences of a Streptococcus mutans cell surface antigen in nonhuman primates. J Immunol. 1989 Oct 15;143(8):2699–2705. [PubMed] [Google Scholar]
  13. Lucero M. E., Kuo C. C. Neutralization of Chlamydia trachomatis cell culture infection by serovar-specific monoclonal antibodies. Infect Immun. 1985 Nov;50(2):595–597. doi: 10.1128/iai.50.2.595-597.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maclean I. W., Peeling R. W., Brunham R. C. Characterization of Chlamydia trachomatis antigens with monoclonal and polyclonal antibodies. Can J Microbiol. 1988 Feb;34(2):141–147. doi: 10.1139/m88-028. [DOI] [PubMed] [Google Scholar]
  15. Mather J. P. Establishment and characterization of two distinct mouse testicular epithelial cell lines. Biol Reprod. 1980 Aug;23(1):243–252. doi: 10.1095/biolreprod23.1.243. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Morrison R. P., Belland R. J., Lyng K., Caldwell H. D. Chlamydial disease pathogenesis. The 57-kD chlamydial hypersensitivity antigen is a stress response protein. J Exp Med. 1989 Oct 1;170(4):1271–1283. doi: 10.1084/jem.170.4.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moulder J. W. Interaction of chlamydiae and host cells in vitro. Microbiol Rev. 1991 Mar;55(1):143–190. doi: 10.1128/mr.55.1.143-190.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Murray E. S., Charbonnet L. T., MacDonald A. B. Immunity to chlamydial infections of the eye. I. The role of circulatory and secretory antibodies in resistance to reinfection with guinea pig inclusion conjunctivitis. J Immunol. 1973 Jun;110(6):1518–1525. [PubMed] [Google Scholar]
  20. Patton D. L., Halbert S. A., Kuo C. C., Wang S. P., Holmes K. K. Host response to primary Chlamydia trachomatis infection of the fallopian tube in pig-tailed monkeys. Fertil Steril. 1983 Dec;40(6):829–840. [PubMed] [Google Scholar]
  21. Patton D. L. Immunopathology and histopathology of experimental chlamydial salpingitis. Rev Infect Dis. 1985 Nov-Dec;7(6):746–753. doi: 10.1093/clinids/7.6.746. [DOI] [PubMed] [Google Scholar]
  22. Ramsey K. H., Rank R. G. Resolution of chlamydial genital infection with antigen-specific T-lymphocyte lines. Infect Immun. 1991 Mar;59(3):925–931. doi: 10.1128/iai.59.3.925-931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ramsey K. H., Soderberg L. S., Rank R. G. Resolution of chlamydial genital infection in B-cell-deficient mice and immunity to reinfection. Infect Immun. 1988 May;56(5):1320–1325. doi: 10.1128/iai.56.5.1320-1325.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rank R. G., Barron A. L. Effect of antithymocyte serum on the course of chlamydial genital infection in female guinea pigs. Infect Immun. 1983 Aug;41(2):876–879. doi: 10.1128/iai.41.2.876-879.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rank R. G., Barron A. L. Humoral immune response in acquired immunity to chlamydial genital infection of female guinea pigs. Infect Immun. 1983 Jan;39(1):463–465. doi: 10.1128/iai.39.1.463-465.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rank R. G., Batteiger B. E., Soderberg L. S. Susceptibility to reinfection after a primary chlamydial genital infection. Infect Immun. 1988 Sep;56(9):2243–2249. doi: 10.1128/iai.56.9.2243-2249.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rank R. G., Ramsey K. H., Pack E. A., Williams D. M. Effect of gamma interferon on resolution of murine chlamydial genital infection. Infect Immun. 1992 Oct;60(10):4427–4429. doi: 10.1128/iai.60.10.4427-4429.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rank R. G., Soderberg L. S., Barron A. L. Chronic chlamydial genital infection in congenitally athymic nude mice. Infect Immun. 1985 Jun;48(3):847–849. doi: 10.1128/iai.48.3.847-849.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rank R. G., Soderberg L. S., Sanders M. M., Batteiger B. E. Role of cell-mediated immunity in the resolution of secondary chlamydial genital infection in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis. Infect Immun. 1989 Mar;57(3):706–710. doi: 10.1128/iai.57.3.706-710.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rice P. A., Schachter J. Pathogenesis of pelvic inflammatory disease. What are the questions? JAMA. 1991 Nov 13;266(18):2587–2593. [PubMed] [Google Scholar]
  31. Selby W. S., Janossy G., Jewell D. P. Immunohistological characterisation of intraepithelial lymphocytes of the human gastrointestinal tract. Gut. 1981 Mar;22(3):169–176. doi: 10.1136/gut.22.3.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shemer-Avni Y., Wallach D., Sarov I. Reversion of the antichlamydial effect of tumor necrosis factor by tryptophan and antibodies to beta interferon. Infect Immun. 1989 Nov;57(11):3484–3490. doi: 10.1128/iai.57.11.3484-3490.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sollid L. M., Brandtzaeg P., Kvale D., Gaudernack G., Scott H., Thorsby E. T cell-epithelium interactions in relation to gut immunity. Monogr Allergy. 1988;24:60–65. [PubMed] [Google Scholar]
  34. Stephens R. S. Challenge of Chlamydia research. Infect Agents Dis. 1992 Dec;1(6):279–293. [PubMed] [Google Scholar]
  35. Taylor H. R., Johnson S. L., Schachter J., Caldwell H. D., Prendergast R. A. Pathogenesis of trachoma: the stimulus for inflammation. J Immunol. 1987 May 1;138(9):3023–3027. [PubMed] [Google Scholar]
  36. Taylor H. R., Prendergast R. A., Dawson C. R., Schachter J., Silverstein A. M. An animal model for cicatrizing trachoma. Invest Ophthalmol Vis Sci. 1981 Sep;21(3):422–433. [PubMed] [Google Scholar]
  37. Wagar E. A., Schachter J., Bavoil P., Stephens R. S. Differential human serologic response to two 60,000 molecular weight Chlamydia trachomatis antigens. J Infect Dis. 1990 Oct;162(4):922–927. doi: 10.1093/infdis/162.4.922. [DOI] [PubMed] [Google Scholar]
  38. Walker P. R., Smerdon R., Haron J., Lehner T. Mapping major and minor T-cell epitopes in vitro and their immunogenic or tolerogenic effect in vivo in non-human primates. Immunology. 1993 Oct;80(2):209–216. [PMC free article] [PubMed] [Google Scholar]
  39. Williams D. M., Bonewald L. F., Roodman G. D., Byrne G. I., Magee D. M., Schachter J. Tumor necrosis factor alpha is a cytotoxin induced by murine Chlamydia trachomatis infection. Infect Immun. 1989 May;57(5):1351–1355. doi: 10.1128/iai.57.5.1351-1355.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Williams D. M., Byrne G. I., Grubbs B., Marshal T. J., Schachter J. Role in vivo for gamma interferon in control of pneumonia caused by Chlamydia trachomatis in mice. Infect Immun. 1988 Nov;56(11):3004–3006. doi: 10.1128/iai.56.11.3004-3006.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Williams D. M., Schachter J., Coalson J. J., Grubbs B. Cellular immunity to the mouse pneumonitis agent. J Infect Dis. 1984 Apr;149(4):630–639. doi: 10.1093/infdis/149.4.630. [DOI] [PubMed] [Google Scholar]
  42. Williams D. M., Schachter J. Role of cell-mediated immunity in chlamydial infection: implications for ocular immunity. Rev Infect Dis. 1985 Nov-Dec;7(6):754–759. doi: 10.1093/clinids/7.6.754. [DOI] [PubMed] [Google Scholar]
  43. Wyrick P. B., Choong J., Davis C. H., Knight S. T., Royal M. O., Maslow A. S., Bagnell C. R. Entry of genital Chlamydia trachomatis into polarized human epithelial cells. Infect Immun. 1989 Aug;57(8):2378–2389. doi: 10.1128/iai.57.8.2378-2389.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zhang Y. X., Stewart S. J., Caldwell H. D. Protective monoclonal antibodies to Chlamydia trachomatis serovar- and serogroup-specific major outer membrane protein determinants. Infect Immun. 1989 Feb;57(2):636–638. doi: 10.1128/iai.57.2.636-638.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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