Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1987 Oct;55(10):2490–2495. doi: 10.1128/iai.55.10.2490-2495.1987

Establishment and characterization of a T-cell line specific for Rickettsia tsutsugamushi.

K Kodama 1, S Kawamura 1, M Yasukawa 1, Y Kobayashi 1
PMCID: PMC260735  PMID: 2443453

Abstract

To study the immunological protective system against rickettsial infection, a T-cell line specific for Rickettsia tsutsugamushi antigen was established by long-term culture of splenocytes from mice immunized with live Gilliam strain R. tsutsugamushi and then propagated in the presence of homologous rickettsial antigen and syngeneic filler cells. The characteristics of the T-cell line and its capacity to induce antirickettsial protection in vivo were studied. Flow cytometric analysis demonstrated that the T-cell line showed the phenotype Thy-1.2+ L3T4+ Lyt-2-, suggestive of helper T cells. In a lymphocyte proliferation assay, this cell line showed a specific response to Gilliam antigen, partial cross-reactivity to Karp antigen, but no response to Kato antigen. The proliferative response of this T-cell line was filler cell dependent, and genetic restriction was observed between the T-cell line and filler cells. The T-cell line produced gamma interferon, one of the macrophage-activating factors, in cultures with specific antigen and was able to adoptively mediate antirickettsial protection in vivo. The data presented here suggest that antigen-specific helper T cells play an important role in protection against rickettsial infection.

Full text

PDF
2490

Selected References

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

  1. Carl M., Dasch G. A. Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors. J Immunol. 1986 Apr 1;136(7):2654–2661. [PubMed] [Google Scholar]
  2. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  3. Jerrells T. R., Osterman J. V. Development of specific and cross-reactive lymphocyte proliferative responses during chronic immunizing infections with Rickettsia tsutsugamushi. Infect Immun. 1983 Apr;40(1):147–156. doi: 10.1128/iai.40.1.147-156.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Jerrells T. R., Osterman J. V. Host defenses in experimental scrub typhus: delayed-type hypersensitivity responses of inbred mice. Infect Immun. 1982 Jan;35(1):117–123. doi: 10.1128/iai.35.1.117-123.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Jerrells T. R., Osterman J. V. Parameters of cellular immunity in acute and chronic Rickettsia tsutsugamushi infections of inbred mice. Adv Exp Med Biol. 1983;162:355–360. doi: 10.1007/978-1-4684-4481-0_33. [DOI] [PubMed] [Google Scholar]
  6. Jerrells T. R., Turco J., Winkler H. H., Spitalny G. L. Neutralization of lymphokine-mediated antirickettsial activity of fibroblasts and macrophages with monoclonal antibody specific for murine interferon gamma. Infect Immun. 1986 Jan;51(1):355–359. doi: 10.1128/iai.51.1.355-359.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  8. Kawamura S. [Immunological studies of Rickettsial infection--experimental Rickettsia tsutsugamushi infection in nude mice]. Kansenshogaku Zasshi. 1984 Jul;58(7):647–662. doi: 10.11150/kansenshogakuzasshi1970.58.647. [DOI] [PubMed] [Google Scholar]
  9. Kenyon R. H., Ascher M. S., Kishimoto R. A., Pedersen C. E., Jr In vitro guinea pig leukocyte reactions to Rickettsia rickettsii. Infect Immun. 1977 Dec;18(3):840–846. doi: 10.1128/iai.18.3.840-846.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kimoto M., Fathman C. G. Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation. J Exp Med. 1980 Oct 1;152(4):759–770. doi: 10.1084/jem.152.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klein J. R., Raulet D. H., Pasternack M. S., Bevan M. J. Cytotoxic T lymphocytes produce immune interferon in response to antigen or mitogen. J Exp Med. 1982 Apr 1;155(4):1198–1203. doi: 10.1084/jem.155.4.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kobayashi Y., Kawamura S., Oyama T. Immunological studies of experimental tsutsugamushi disease in congenitally athymic (nude) mice. Am J Trop Med Hyg. 1985 May;34(3):568–577. doi: 10.4269/ajtmh.1985.34.568. [DOI] [PubMed] [Google Scholar]
  13. Kobayashi Y., Tachibana N. Purification of complement-fixing antigen of Rickettsia orientalis. J Immunol. 1965 Sep;95(3):412–417. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Landolfo S., Kirchner H., Simon M. M. Production of immune interferon is regulated by more than T cell subset: Lyt-1,2,3 and Qat-5 phenotypes of murine T lymphocytes involved in IFN-gamma production in primary and secondary mixed lymphocyte reaction. Eur J Immunol. 1982 Apr;12(4):295–299. doi: 10.1002/eji.1830120408. [DOI] [PubMed] [Google Scholar]
  16. Marrack P., Endres R., Shimonkevitz R., Zlotnik A., Dialynas D., Fitch F., Kappler J. The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product. J Exp Med. 1983 Oct 1;158(4):1077–1091. doi: 10.1084/jem.158.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morris A. G., Lin Y. L., Askonas B. A. Immune interferon release when a cloned cytotoxic T-cell line meets its correct influenza-infected target cell. Nature. 1982 Jan 14;295(5845):150–152. doi: 10.1038/295150a0. [DOI] [PubMed] [Google Scholar]
  18. Nacy C. A., Meltzer M. S. Macrophages in resistance to rickettsial infection: macrophage activation in vitro for killing of Rickettsia tsutsugamushi. J Immunol. 1979 Dec;123(6):2544–2549. [PubMed] [Google Scholar]
  19. Nacy C. A., Meltzer M. S. Macrophages in resistance to rickettsial infection: strains of mice susceptible to the lethal effects of Rickettsia akari show defective macrophage Rickettsicidal activity in vitro. Infect Immun. 1982 Jun;36(3):1096–1101. doi: 10.1128/iai.36.3.1096-1101.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nacy C. A., Meltzer M. S. Macrophages in resistance to rickettsial infections: protection against lethal Rickettsia tsutsugamushi infections by treatment of mice with macrophage-activating agents. J Leukoc Biol. 1984 Apr;35(4):385–396. doi: 10.1002/jlb.35.4.385. [DOI] [PubMed] [Google Scholar]
  21. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Osterman J. V. Rickettsiae and hosts. Acta Virol. 1985 Mar;29(2):166–173. [PubMed] [Google Scholar]
  23. Palmer B. A., Hetrick F. M., Jerrells T. J. Production of gamma interferon in mice immune to Rickettsia tsutsugamushi. Infect Immun. 1984 Jan;43(1):59–65. doi: 10.1128/iai.43.1.59-65.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Palmer B. A., Hetrick F. M., Jerrells T. R. Gamma interferon production in response to homologous and heterologous strain antigens in mice chronically infected with Rickettsia tsutsugamushi. Infect Immun. 1984 Oct;46(1):237–244. doi: 10.1128/iai.46.1.237-244.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rollwagen F. M., Bakun A. J., Dorsey C. H., Dasch G. A. Mechanisms of immunity to infection with typhus rickettsiae: infected fibroblasts bear rickettsial antigens on their surfaces. Infect Immun. 1985 Dec;50(3):911–916. doi: 10.1128/iai.50.3.911-916.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rollwagen F. M., Dasch G. A., Jerrells T. R. Mechanisms of immunity to rickettsial infection: characterization of a cytotoxic effector cell. J Immunol. 1986 Feb 15;136(4):1418–1421. [PubMed] [Google Scholar]
  27. Shirai A., Catanzaro P. J., Phillips S. M., Osterman J. V. Host defenses in experimental scrub typhus: role of cellular immunity in heterologous protection. Infect Immun. 1976 Jul;14(1):39–46. doi: 10.1128/iai.14.1.39-46.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith K. A., Ruscetti F. W. T-cell growth factor and the culture of cloned functional T cells. Adv Immunol. 1981;31:137–175. doi: 10.1016/s0065-2776(08)60920-7. [DOI] [PubMed] [Google Scholar]
  29. Sredni B., Tse H. Y., Chen C., Schwartz R. H. Antigen-specific clones of proliferating T lymphocytes. I. Methodology, specificity, and MHC restriction. J Immunol. 1981 Jan;126(1):341–347. [PubMed] [Google Scholar]
  30. Turco J., Winkler H. H. Comparison of the properties of antirickettsial activity and interferon in mouse lymphokines. Infect Immun. 1983 Oct;42(1):27–32. doi: 10.1128/iai.42.1.27-32.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Turco J., Winkler H. H. Inhibition of the growth of Rickettsia prowazekii in cultured fibroblasts by lymphokines. J Exp Med. 1983 Mar 1;157(3):974–986. doi: 10.1084/jem.157.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  33. Wisseman C. L., Jr, Waddell A. Interferonlike factors from antigen- and mitogen-stimulated human leukocytes with antirickettsial and cytolytic actions on Rickettsia prowazekii. Infected human endothelial cells, fibroblasts, and macrophages. J Exp Med. 1983 Jun 1;157(6):1780–1793. doi: 10.1084/jem.157.6.1780. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES