Abstract
Chlamydiae are a major cause of infertility and preventable blindness and there is currently no effective vaccine in humans or rodents against these organisms. We have previously shown that a peptide of 12 amino acids (termed TINKP) from a conserved region of the major outer membrane protein (MOMP) of Chlamydia trachomatis (C. trachomatis) is a primary T-cell epitope in humans. Here we showed that when dendritic cells (DC) from C3H or BALB/c mice were pulsed in vitro with the peptide they stimulated proliferation of syngeneic T cells in vitro indicating that the peptide is also a primary T-cell epitope in mice. Since the skin is a rich source of DC, we immunized mice from each strain with an intradermal injection of the peptide. Humoral and cell-mediated immunity to peptide, MOMP or whole elementary bodies (EB) of C. trachomatis (F/NI1/GU) were assessed. No antibody response to TINKP was observed. However, immunized mice showed recall responses to all three chlamydial antigens. T-cell-mediated immunity in the absence of antibody was induced by a single injection of the peptide intradermally. C. trachomatis isolated from the human genital tract causes salpingitis in mice. Preliminary studies in susceptible C3H mice indicated that intradermal injection of peptide conferred some protection against the development of salpingitis. Thus, a primary T-cell epitope identified by in vitro stimulation using DC can also initiate cell-mediated immunity in vivo and this approach may be useful in the development of vaccines.
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- 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]
- Allen J. E., Stephens R. S. An intermolecular mechanism of T cell help for the production of antibodies to the bacterial pathogen, Chlamydia trachomatis. Eur J Immunol. 1993 May;23(5):1169–1172. doi: 10.1002/eji.1830230529. [DOI] [PubMed] [Google Scholar]
- Bailey R. L., Kajbaf M., Whittle H. C., Ward M. E., Mabey D. C. The influence of local antichlamydial antibody on the acquisition and persistence of human ocular chlamydial infection: IgG antibodies are not protective. Epidemiol Infect. 1993 Oct;111(2):315–324. doi: 10.1017/s0950268800057022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barenfanger J., MacDonald A. B. The role of immunoglobulin in the neutralization of trachoma infectivity. J Immunol. 1974 Nov;113(5):1607–1617. [PubMed] [Google Scholar]
- Byrne G. I., Grubbs B., Marshall T. J., Schachter J., Williams D. M. Gamma interferon-mediated cytotoxicity related to murine Chlamydia trachomatis infection. Infect Immun. 1988 Aug;56(8):2023–2027. doi: 10.1128/iai.56.8.2023-2027.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Bruijn M. L., Nieland J. D., Schumacher T. N., Ploegh H. L., Kast W. M., Melief C. J. Mechanisms of induction of primary virus-specific cytotoxic T lymphocyte responses. Eur J Immunol. 1992 Nov;22(11):3013–3020. doi: 10.1002/eji.1830221137. [DOI] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ishizaki M., Allen J. E., Beatty P. R., Stephens R. S. Immune specificity of murine T-cell lines to the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1992 Sep;60(9):3714–3718. doi: 10.1128/iai.60.9.3714-3718.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knight S. C., Krejci J., Malkovsky M., Colizzi V., Gautam A., Asherson G. L. The role of dendritic cells in the initiation of immune responses to contact sensitizers. I. In vivo exposure to antigen. Cell Immunol. 1985 Sep;94(2):427–434. doi: 10.1016/0008-8749(85)90266-7. [DOI] [PubMed] [Google Scholar]
- Landers D. V., Erlich K., Sung M., Schachter J. Role of L3T4-bearing T-cell populations in experimental murine chlamydial salpingitis. Infect Immun. 1991 Oct;59(10):3774–3777. doi: 10.1128/iai.59.10.3774-3777.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Macatonia S. E., Patterson S., Knight S. C. Primary proliferative and cytotoxic T-cell responses to HIV induced in vitro by human dendritic cells. Immunology. 1991 Nov;74(3):399–406. [PMC free article] [PubMed] [Google Scholar]
- Macatonia S. E., Taylor P. M., Knight S. C., Askonas B. A. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. doi: 10.1084/jem.169.4.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Magee D. M., Smith J. G., Bleicker C. A., Carter C. J., Bonewald L. F., Schachter J., Williams D. M. Chlamydia trachomatis pneumonia induces in vivo production of interleukin-1 and -6. Infect Immun. 1992 Mar;60(3):1217–1220. doi: 10.1128/iai.60.3.1217-1220.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Nichols R. L., Oertley R. E., Fraser E. C., MacDonald A. B., McComb D. E. Immunity to chlamydial infections of the eye. VI. Homologous neutralization of trachoma infectivity for the owl monkey conjuctivae by eye secretions from humans with trachoma. J Infect Dis. 1973 Apr;127(4):429–432. doi: 10.1093/infdis/127.4.429. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Sowa S., Sowa J., Collier L. H., Blyth W. A. Trachoma vaccine field trials in The Gambia. J Hyg (Lond) 1969 Dec;67(4):699–717. doi: 10.1017/s0022172400042157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Steinman R. M., Gutchinov B., Witmer M. D., Nussenzweig M. C. Dendritic cells are the principal stimulators of the primary mixed leukocyte reaction in mice. J Exp Med. 1983 Feb 1;157(2):613–627. doi: 10.1084/jem.157.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su H., Caldwell H. D. Immunogenicity of a synthetic oligopeptide corresponding to antigenically common T-helper and B-cell neutralizing epitopes of the major outer membrane protein of Chlamydia trachomatis. Vaccine. 1993;11(11):1159–1166. doi: 10.1016/0264-410x(93)90080-h. [DOI] [PubMed] [Google Scholar]
- Tuffrey M., Alexander F., Conlan W., Woods C., Ward M. Heterotypic protection of mice against chlamydial salpingitis and colonization of the lower genital tract with a human serovar F isolate of Chlamydia trachomatis by prior immunization with recombinant serovar L1 major outer-membrane protein. J Gen Microbiol. 1992 Aug;138(Pt 8):1707–1715. doi: 10.1099/00221287-138-8-1707. [DOI] [PubMed] [Google Scholar]
- Tuffrey M., Alexander F., Inman C., Ward M. E. Correlation of infertility with altered tubal morphology and function in mice with salpingitis induced by a human genital-tract isolate of Chlamydia trachomatis. J Reprod Fertil. 1990 Jan;88(1):295–305. doi: 10.1530/jrf.0.0880295. [DOI] [PubMed] [Google Scholar]
- Tuffrey M., Alexander F., Taylor-Robinson D. Severity of salpingitis in mice after primary and repeated inoculation with a human strain of Chlamydia trachomatis. J Exp Pathol (Oxford) 1990 Jun;71(3):403–410. [PMC free article] [PubMed] [Google Scholar]
- Zhang Y. X., Stewart S., Joseph T., Taylor H. R., Caldwell H. D. Protective monoclonal antibodies recognize epitopes located on the major outer membrane protein of Chlamydia trachomatis. J Immunol. 1987 Jan 15;138(2):575–581. [PubMed] [Google Scholar]