Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1990 Feb;58(2):495–501. doi: 10.1128/iai.58.2.495-501.1990

Induction of antigen-specific immunity and tolerance to Mycobacterium leprae in Lewis rats.

M A Winters 1, R C Humphres 1
PMCID: PMC258484  PMID: 2404873

Abstract

Intradermal (i.d.) immunization of Lewis rats with autoclaved Mycobacterium leprae resulted in antigen-specific proliferation responses and interleukin-2 release from spleen and lymph node cells that were detectable as early as 21 days, persisted for at least 9 months, and were dependent on the dose of antigen administered. Immunized animals were also completely resistant to a footpad challenge with viable M. leprae. In contrast, intravenous (i.v.) administration of at least 10(8) irradiated M. leprae isolates induced a state of nonresponsiveness characterized by the absence of proliferation and interleukin-2 release by antigen-stimulated lymphoid cell cultures; however, in vitro responses to mitogenic stimulation and in vivo responses to keyhole limpet hemocyanin and Listeria monocytogenes were normal. Animals that received an i.v. injection of M. leprae remained nonresponsive to M. leprae antigens even after a subsequent i.d. immunization. This state of nonresponsiveness persisted for at least 6 months after induction. Results of footpad challenge experiments showed that the ability of animals rendered nonresponsive by an i.v. injection of M. leprae to control the growth of viable M. leprae in the footpad was not different from that of untreated rats. In addition, animals receiving an initial i.v. injection and a subsequent i.d. immunization with M. leprae were not protected from a viable challenge, as were rats that received only i.d. immunization. These results suggest that i.v. administration of a large dose of M. leprae to rats induces a state of nonresponsiveness to M. leprae antigens that may be similar to that seen in lepromatous leprosy patients.

Full text

PDF
495

Selected References

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

  1. Bjune G., Barnetson R. S., Ridley D. S., Kronvall G. Lymphocyte transformation test in leprosy; correlation of the response with inflammation of lesions. Clin Exp Immunol. 1976 Jul;25(1):85–94. [PMC free article] [PubMed] [Google Scholar]
  2. Bjune G. In vitro lymphocyte stimulation in leprosy; simultaneous stimulation with Mycobacterium leprae antigens and phytohaemagglutinin. Clin Exp Immunol. 1979 Jun;36(3):479–487. [PMC free article] [PubMed] [Google Scholar]
  3. Dawson P. J., Colston M. J., Fieldsteel A. H. Infection of the congenitally athymic rat with Mycobacterium leprae. Int J Lepr Other Mycobact Dis. 1983 Sep;51(3):336–346. [PubMed] [Google Scholar]
  4. Fieldsteel A. H., McIntosh A. H. Effect of neonatal thymectomy and antithymocytic serum on susceptibility of rats to mycobacterium leprae infection. Proc Soc Exp Biol Med. 1971 Nov;138(2):408–413. doi: 10.3181/00379727-138-35908. [DOI] [PubMed] [Google Scholar]
  5. Haregewoin A., Godal T., Mustafa A. S., Belehu A., Yemaneberhan T. T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy. Nature. 1983 May 26;303(5915):342–344. doi: 10.1038/303342a0. [DOI] [PubMed] [Google Scholar]
  6. Harris D. P., Jones A. G., Wade S., Krahenbuhl J. L., Gillis T. P., Watson J. D. Genetic control of murine T cell proliferative responses to Mycobacterium leprae. V. Evidence for cross-reactivity between host antigens and Mycobacterium leprae. J Immunol. 1988 Sep 1;141(5):1695–1700. [PubMed] [Google Scholar]
  7. Hirschberg H. The role of macrophages in the lymphoproliferative response to Mycobacterium leprae in vitro. Clin Exp Immunol. 1978 Oct;34(1):46–51. [PMC free article] [PubMed] [Google Scholar]
  8. Mehra V., Brennan P. J., Rada E., Convit J., Bloom B. R. Lymphocyte suppression in leprosy induced by unique M. leprae glycolipid. Nature. 1984 Mar 8;308(5955):194–196. doi: 10.1038/308194a0. [DOI] [PubMed] [Google Scholar]
  9. Mehra V., Convit J., Rubinstein A., Bloom B. R. Activated suppressor T cells in leprosy. J Immunol. 1982 Nov;129(5):1946–1951. [PubMed] [Google Scholar]
  10. Mehra V., Mason L. H., Fields J. P., Bloom B. R. Lepromin-induced suppressor cells in patients with leprosy. J Immunol. 1979 Oct;123(4):1813–1817. [PubMed] [Google Scholar]
  11. Mehra V., Mason L. H., Rothman W., Reinherz E., Schlossman S. F., Bloom B. R. Delineation of a human T cell subset responsible for lepromin-induced suppression in leprosy patients. J Immunol. 1980 Sep;125(3):1183–1188. [PubMed] [Google Scholar]
  12. Modlin R. L., Kato H., Mehra V., Nelson E. E., Fan X. D., Rea T. H., Pattengale P. K., Bloom B. R. Genetically restricted suppressor T-cell clones derived from lepromatous leprosy lesions. 1986 Jul 31-Aug 6Nature. 322(6078):459–461. doi: 10.1038/322459a0. [DOI] [PubMed] [Google Scholar]
  13. Mohagheghpour N., Gelber R. H., Larrick J. W., Sasaki D. T., Brennan P. J., Engleman E. G. Defective cell-mediated immunity in leprosy: failure of T cells from lepromatous leprosy patients to respond to Mycobacterium leprae is associated with defective expression of interleukin 2 receptors and is not reconstituted by interleukin 2. J Immunol. 1985 Aug;135(2):1443–1449. [PubMed] [Google Scholar]
  14. Mohagheghpour N., Gelber R. R., Engleman E. G. T cell defect in lepromatous leprosy is reversible in vitro in the absence of exogenous growth factors. J Immunol. 1987 Jan 15;138(2):570–574. [PubMed] [Google Scholar]
  15. Myrvang B., Godal T., Ridley D. S., Fröland S. S., Song Y. K. Immune responsiveness to Mycobacterium leprae and other mycobacterial antigens throughout the clinical and histopathological spectrum of leprosy. Clin Exp Immunol. 1973 Aug;14(4):541–553. [PMC free article] [PubMed] [Google Scholar]
  16. Ottenhoff T. H., Elferink D. G., Klatser P. R., de Vries R. R. Cloned suppressor T cells from a lepromatous leprosy patient suppress Mycobacterium leprae reactive helper T cells. 1986 Jul 31-Aug 6Nature. 322(6078):462–464. doi: 10.1038/322462a0. [DOI] [PubMed] [Google Scholar]
  17. Rees R. J. The impact of experimental human leprosy in the mouse on leprosy research. Int J Lepr Other Mycobact Dis. 1971 Apr-Jun;39(2):201–215. [PubMed] [Google Scholar]
  18. Sansonetti P., Lagrange P. H. The immunology of leprosy: speculations on the leprosy spectrum. Rev Infect Dis. 1981 May-Jun;3(3):422–469. doi: 10.1093/clinids/3.3.422. [DOI] [PubMed] [Google Scholar]
  19. Shepard C. C., McRae D. H. A method for counting acid-fast bacteria. Int J Lepr Other Mycobact Dis. 1968 Jan-Mar;36(1):78–82. [PubMed] [Google Scholar]
  20. Shepard C. C., Minagawa F., Van Landingham R., Walker L. L. Foot pad enlargement as a measure of induced immunity to Mycobacterium leprae. Int J Lepr Other Mycobact Dis. 1980 Dec;48(4):371–381. [PubMed] [Google Scholar]
  21. Shepard C. C., Walker L. L., Van Landingham R. M., Ye S. Z. Sensitization or tolerance to Mycobacterium leprae antigen by route of injection. Infect Immun. 1982 Nov;38(2):673–680. doi: 10.1128/iai.38.2.673-680.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shepard C. C., van Landingham R. M., Walker L. L., Ye S. Z. Comparison of the immunogenicity of vaccines prepared from viable Mycobacterium bovis BCG, heat-killed Mycobacterium leprae, and a mixture of the two for normal and M. leprae-tolerant mice. Infect Immun. 1983 Jun;40(3):1096–1103. doi: 10.1128/iai.40.3.1096-1103.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sibley L. D., Krahenbuhl J. L. Mycobacterium leprae-burdened macrophages are refractory to activation by gamma interferon. Infect Immun. 1987 Feb;55(2):446–450. doi: 10.1128/iai.55.2.446-450.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES