Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Jun;64(6):1944–1949. doi: 10.1128/iai.64.6.1944-1949.1996

Cytotoxic-T-lymphocyte-mediated cytolysis of L cells persistently infected with Chlamydia spp.

S J Rasmussen 1, P Timms 1, P R Beatty 1, R S Stephens 1
PMCID: PMC174020  PMID: 8675291

Abstract

Persistent chlamydial infections have been proposed as a means whereby chlamydiae evade immune resolution of infection. Such a mechanism would require evasion not only of the humoral immune responses but also of cell-mediated immune responses. We hypothesized that if such a mechanism is important, persistently infected cells should not be recognized by cytotoxic T cells. Persistent infections were simulated in vitro by treatment of Chlamydia trachomatis- or Chlamydia psittaci-infected cells with gamma interferon (IFN-gamma), penicillin, or tryptophan depletion. Cultures were examined for induction of a chlamydial stress response (measured by transcription of groesl RNA) and for the effects on viability, infectivity, morphology, and immune recognition. Although both IFN-gamma and penicillin induced aberrant chlamydial morphology and growth, we did not find evidence that these treatments elicited a classical stress response. In addition, T-cell-mediated lysis of Chlamydia-infected target cells treated with IFN-gamma or penicillin or grown in tryptophan-deficient media was examined. The immune cell-mediated lysis of these treated infected cells demonstrated that despite the effects of these compounds on chlamydial growth and development, the infected cells continued to be efficiently recognized and killed by cytotoxic T cells. Thus, it seems unlikely that these in vitro models of persistence represent functional mechanisms to evade immune clearance.

Full Text

The Full Text of this article is available as a PDF (294.4 KB).

Selected References

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

  1. Allan I., Pearce J. H. Amino acid requirements of strains of Chlamydia trachomatis and C. psittaci growing in McCoy cells: relationship with clinical syndrome and host origin. J Gen Microbiol. 1983 Jul;129(7):2001–2007. doi: 10.1099/00221287-129-7-2001. [DOI] [PubMed] [Google Scholar]
  2. Arno J. N., Ricker V. A., Batteiger B. E., Katz B. P., Caine V. A., Jones R. B. Interferon-gamma in endocervical secretions of women infected with Chlamydia trachomatis. J Infect Dis. 1990 Dec;162(6):1385–1389. doi: 10.1093/infdis/162.6.1385. [DOI] [PubMed] [Google Scholar]
  3. Beatty P. R., Stephens R. S. CD8+ T lymphocyte-mediated lysis of Chlamydia-infected L cells using an endogenous antigen pathway. J Immunol. 1994 Nov 15;153(10):4588–4595. [PubMed] [Google Scholar]
  4. Beatty P. R., Stephens R. S. Identification of Chlamydia trachomatis antigens by use of murine T-cell lines. Infect Immun. 1992 Nov;60(11):4598–4603. doi: 10.1128/iai.60.11.4598-4603.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beatty W. L., Belanger T. A., Desai A. A., Morrison R. P., Byrne G. I. Tryptophan depletion as a mechanism of gamma interferon-mediated chlamydial persistence. Infect Immun. 1994 Sep;62(9):3705–3711. doi: 10.1128/iai.62.9.3705-3711.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beatty W. L., Byrne G. I., Morrison R. P. Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3998–4002. doi: 10.1073/pnas.90.9.3998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beatty W. L., Morrison R. P., Byrne G. I. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev. 1994 Dec;58(4):686–699. doi: 10.1128/mr.58.4.686-699.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buxton D., Barlow R. M., Finlayson J., Anderson I. E., Mackellar A. Observations on the pathogenesis of Chlamydia psittaci infection of pregnant sheep. J Comp Pathol. 1990 Feb;102(2):221–237. [PubMed] [Google Scholar]
  9. Byrne G. I., Schobert C. S., Williams D. M., Krueger D. A. Characterization of gamma interferon-mediated cytotoxicity to chlamydia-infected fibroblasts. Infect Immun. 1989 Mar;57(3):870–874. doi: 10.1128/iai.57.3.870-874.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  11. Coles A. M., Reynolds D. J., Harper A., Devitt A., Pearce J. H. Low-nutrient induction of abnormal chlamydial development: a novel component of chlamydial pathogenesis? FEMS Microbiol Lett. 1993 Jan 15;106(2):193–200. doi: 10.1111/j.1574-6968.1993.tb05958.x. [DOI] [PubMed] [Google Scholar]
  12. Engel J. N., Pollack J., Perara E., Ganem D. Heat shock response of murine Chlamydia trachomatis. J Bacteriol. 1990 Dec;172(12):6959–6972. doi: 10.1128/jb.172.12.6959-6972.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hatch T. P. Competition between Chlamydia psittaci and L cells for host isoleucine pools: a limiting factor in chlamydial multiplication. Infect Immun. 1975 Jul;12(1):211–220. doi: 10.1128/iai.12.1.211-220.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kaufmann S. H. CD8+ T lymphocytes in intracellular microbial infections. Immunol Today. 1988 Jun;9(6):168–174. doi: 10.1016/0167-5699(88)91292-3. [DOI] [PubMed] [Google Scholar]
  15. Kurlander R. J., Shawar S. M., Brown M. L., Rich R. R. Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. Science. 1992 Jul 31;257(5070):678–679. doi: 10.1126/science.1496381. [DOI] [PubMed] [Google Scholar]
  16. Magee D. M., Williams D. M., Smith J. G., Bleicker C. A., Grubbs B. G., Schachter J., Rank R. G. Role of CD8 T cells in primary Chlamydia infection. Infect Immun. 1995 Feb;63(2):516–521. doi: 10.1128/iai.63.2.516-521.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mayer J., Woods M. L., Vavrin Z., Hibbs J. B., Jr Gamma interferon-induced nitric oxide production reduces Chlamydia trachomatis infectivity in McCoy cells. Infect Immun. 1993 Feb;61(2):491–497. doi: 10.1128/iai.61.2.491-497.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Monnickendam M. A., Darougar S., Treharne J. D., Tilbury A. M. Development of chronic conjunctivitis with scarring and pannus, resembling trachoma, in guinea-pigs. Br J Ophthalmol. 1980 Apr;64(4):284–290. doi: 10.1136/bjo.64.4.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pollard D. R., Tyler S. D., Ng C. W., Rozee K. R. A polymerase chain reaction (PCR) protocol for the specific detection of Chlamydia spp. Mol Cell Probes. 1989 Dec;3(4):383–389. doi: 10.1016/0890-8508(89)90017-0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Rasmussen S., Timms P. Detection of Chlamydia psittaci using DNA probes and the polymerase chain reaction. FEMS Microbiol Lett. 1991 Jan 15;61(2-3):169–173. doi: 10.1016/0378-1097(91)90546-m. [DOI] [PubMed] [Google Scholar]
  24. Schachter J., Moncada J., Dawson C. R., Sheppard J., Courtright P., Said M. E., Zaki S., Hafez S. F., Lorincz A. Nonculture methods for diagnosing chlamydial infection in patients with trachoma: a clue to the pathogenesis of the disease? J Infect Dis. 1988 Dec;158(6):1347–1352. doi: 10.1093/infdis/158.6.1347. [DOI] [PubMed] [Google Scholar]
  25. Stagg A. J., Elsley W. A., Pickett M. A., Ward M. E., Knight S. C. Primary human T-cell responses to the major outer membrane protein of Chlamydia trachomatis. Immunology. 1993 May;79(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  26. Starnbach M. N., Bevan M. J., Lampe M. F. Protective cytotoxic T lymphocytes are induced during murine infection with Chlamydia trachomatis. J Immunol. 1994 Dec 1;153(11):5183–5189. [PubMed] [Google Scholar]
  27. Tamura A., Manire G. P. Effect of penicillin on the multiplication of meningopneumonitis organisms (Chlamydia psittaci). J Bacteriol. 1968 Oct;96(4):875–880. doi: 10.1128/jb.96.4.875-880.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Taylor M. W., Feng G. S. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991 Aug;5(11):2516–2522. [PubMed] [Google Scholar]
  29. Yang Z. P., Cummings P. K., Patton D. L., Kuo C. C. Ultrastructural lung pathology of experimental Chlamydia pneumoniae pneumonitis in mice. J Infect Dis. 1994 Aug;170(2):464–467. doi: 10.1093/infdis/170.2.464. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES