Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Mar 1;153(3):557–568. doi: 10.1084/jem.153.3.557

Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to leishmania tropica

JG Howard, C Hale, FY Liew
PMCID: PMC2186105  PMID: 6454739

Abstract

The overwhelming susceptibility of BALB/c mice to infection with Leishmania tropica can be substantially reversed by immediately prior sub-lethal irradiation. This is related to radiation dosage, and at 550 rad, causes 60 percent complete cures and only 19 percent (instead of 100 percent) incidence of progressive disease. Irradiation 10 d before infection is only weakly prophylactic, whereas 10 d after is without effect. Control of lesion development is only apparent after the first 30 d, coincident with the analogous onset previously found in resistant strains and adult thymectomized, x-irradiated, bone marrow-reconstituted BALB/c mice. Instead of the specific suppression of DTH characteristic of L. tropica infection in the BALB/c strain, healed irradiated mice express strong anti-leishmanial DTH reactivity and resistance to reinfection. T cells from these mice transfer DTH reactivity which is suppressed by admixture with cells from nonhealed, nonreactive donors. Irradiated BALB/c mice again develop inexorable disease progression, after its transient arrest, when they are reconstituted with normal T cells. When the T cells are derived from uncontrollably-infected donors, the susceptibility regained is indistinguishable from that of normal mice. B cells do not modify the prophylactic effect of 550 rad, whereas T cells from healed mice confer strong protective immunity throughout the initial phase. Regression or progression of disease correlates completely with DTH reactivity in all these groups. Although BALB/c mice express an extreme level of genetic susceptibility to L. tropica infection, they are nevertheless capable of mounting a curative cell mediated immune response. That this is ineffective during pathogenesis of the disease was previously associated correlatively with potent specific suppressor T cell generation, which is now shown to be preventable by prior irradiation. Most important, however, a causal role for these cells in vivo has been demonstrated directly by reconstitution.

Full Text

The Full Text of this article is available as a PDF (828.3 KB).

Selected References

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

  1. Allain D. S., Kagan I. G. An evaluation of the direct agglutination test for Chagas' disease. J Parasitol. 1974 Feb;60(1):179–184. [PubMed] [Google Scholar]
  2. Behin R., Mauel J., Sordat B. Leishmania tropica: pathogenicity and in vitro macrophage function in strains of inbred mice. Exp Parasitol. 1979 Aug;48(1):81–91. doi: 10.1016/0014-4894(79)90057-2. [DOI] [PubMed] [Google Scholar]
  3. Bradley D. J. Regulation of Leishmania populations within the host. II. genetic control of acute susceptibility of mice to Leishmania donovani infection. Clin Exp Immunol. 1977 Oct;30(1):130–140. [PMC free article] [PubMed] [Google Scholar]
  4. Bradley D. J., Taylor B. A., Blackwell J., Evans E. P., Freeman J. Regulation of Leishmania populations within the host. III. Mapping of the locus controlling susceptibility to visceral leishmaniasis in the mouse. Clin Exp Immunol. 1979 Jul;37(1):7–14. [PMC free article] [PubMed] [Google Scholar]
  5. Bryceson A. D., Bray R. S., Wolstencroft R. A., Dumonde D. C. Immunity in cutaneous leishmaniasis of the guinea-pig. Clin Exp Immunol. 1970 Sep;7(3):301–341. [PMC free article] [PubMed] [Google Scholar]
  6. Buchmüller Y., Mauel J. Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes. J Exp Med. 1979 Aug 1;150(2):359–370. doi: 10.1084/jem.150.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FISHMAN M., SCHECHMEISTER I. L. The effect of ionizing radiation on phagocytosis and the bactericidal power of the blood. II. The effect of radiation on ingestion and digestion of bacteria. J Exp Med. 1955 Mar 1;101(3):275–290. doi: 10.1084/jem.101.3.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Handman E., Ceredig R., Mitchell G. F. Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. Aust J Exp Biol Med Sci. 1979 Feb;57(1):9–29. doi: 10.1038/icb.1979.2. [DOI] [PubMed] [Google Scholar]
  9. Howard J. G., Hale C., Chan-Liew W. L. Immunological regulation of experimental cutaneous leishmaniasis. 1. Immunogenetic aspects of susceptibility to Leishmania tropica in mice. Parasite Immunol. 1980 Winter;2(4):303–314. doi: 10.1111/j.1365-3024.1980.tb00061.x. [DOI] [PubMed] [Google Scholar]
  10. Howard J. G., Hale C., Liew F. Y. Genetically determined susceptibility to Leishmania tropica infection is expressed by haematopoietic donor cells in mouse radiation chimaeras. Nature. 1980 Nov 13;288(5787):161–162. doi: 10.1038/288161a0. [DOI] [PubMed] [Google Scholar]
  11. Howard J. G., Hale C., Liew F. Y. Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica. J Exp Med. 1980 Sep 1;152(3):594–607. doi: 10.1084/jem.152.3.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KENNEDY J. C., TILL J. E., SIMINOVITCH L., MCCULLOCH E. A. RADIOSENSITIVITY OF THE IMMUNE RESPONSE TO SHEEP RED CELLS IN THE MOUSE, AS MEASURED BY THE HEMOLYTIC PLAQUE METHOD. J Immunol. 1965 May;94:715–722. [PubMed] [Google Scholar]
  13. Liew F. Y. Regulation of delayed-type hypersensitivity. I. T suppressor cells for delayed-type hypersensitivity to sheep erythrocytes in mice. Eur J Immunol. 1977 Oct;7(10):714–718. doi: 10.1002/eji.1830071013. [DOI] [PubMed] [Google Scholar]
  14. Mauel J., Buchmüller Y., Behin R. Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes. J Exp Med. 1978 Aug 1;148(2):393–407. doi: 10.1084/jem.148.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McCullagh P. Radiosensitivity of suppressor cells in newborn rats. Aust J Exp Biol Med Sci. 1976 Oct;53(5):399–411. doi: 10.1038/icb.1975.45. [DOI] [PubMed] [Google Scholar]
  16. Mitchell G. F., Curtis J. M., Handman E., McKenzie I. F. Cutaneous leishmaniasis in mice: disease patterns in reconstituted nude mice of several genotypes infected with Leishmania tropica. Aust J Exp Biol Med Sci. 1980 Oct;58(5):521–532. doi: 10.1038/icb.1980.54. [DOI] [PubMed] [Google Scholar]
  17. NEAL R. A. CHEMOTHERAPY OF CUTANEOUS LEISHMANIASIS: LEISHMANIA TROPICA INFECTIONS IN MICE. Ann Trop Med Parasitol. 1964 Dec;58:420–430. doi: 10.1080/00034983.1964.11686264. [DOI] [PubMed] [Google Scholar]
  18. NELSON E. L., BECKER J. R. The effect of whole-body x irradiation on the bactericidal activity of pagocytic cells. II. Survival of Pseudomonas aeruginosa within livers and spleens of mice. J Infect Dis. 1959 Jan-Feb;104(1):20–23. doi: 10.1093/infdis/104.1.20. [DOI] [PubMed] [Google Scholar]
  19. Nasseri M., Modabber F. Z. Generalized infection and lack of delayed hypersensitivity in BALB/c mice infected with Leishmania tropica major. Infect Immun. 1979 Nov;26(2):611–614. doi: 10.1128/iai.26.2.611-614.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Preston P. M., Behbehani K., Dumonde D. C. Experimental cutaneous leishmaniasis: VI: anergy and allergy in the cellular immune response during non-healing infection in different strains of mice. J Clin Lab Immunol. 1978 Nov;1(3):207–219. [PubMed] [Google Scholar]
  21. Preston P. M., Carter R. L., Leuchars E., Davies A. J., Dumonde D. C. Experimental cutaneous leishmaniasis. 3. Effects of thymectomy on the course of infection of CBA mice with Leishmania tropica. Clin Exp Immunol. 1972 Feb;10(2):337–357. [PMC free article] [PubMed] [Google Scholar]
  22. Ramshaw I. A., Bretscher P. A., Parish C. R. Regulation of the immune response. I. Suppression of delayed-type hypersensitivity by T cells from mice expressing humoral immunity. Eur J Immunol. 1976 Oct;6(10):674–679. doi: 10.1002/eji.1830061003. [DOI] [PubMed] [Google Scholar]
  23. Sabbadini E. Regulation of cell-mediated cytotoxicity. I. Augmentation of cell-mediated cytotoxicity induced by radiation. J Exp Med. 1974 Aug 1;140(2):470–480. doi: 10.1084/jem.140.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weintraub J., Weinbaum F. I. The effect of BCG on experimental cutaneous leishmaniasis in mice. J Immunol. 1977 Jun;118(6):2288–2290. [PubMed] [Google Scholar]
  25. Zembala M., Asherson G. L. The effect of cyclophosphamide and irradiation on cells which suppress contact sensitivity in the mouse. Clin Exp Immunol. 1976 Mar;23(3):554–561. [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES