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. 1987 Mar;55(3):645–651. doi: 10.1128/iai.55.3.645-651.1987

Induction of delayed-type hypersensitivity to Leishmania major and the concomitant acceleration of disease development in progressive murine cutaneous leishmaniasis.

J S Dhaliwal, F Y Liew
PMCID: PMC260388  PMID: 3818088

Abstract

BALB/c mice injected intradermally with 10(5) or higher doses of formaldehyde-fixed promastigotes (FFP) of Leishmania major developed strong delayed-type hypersensitivity (DTH) to leishmanial antigens injected into the hind footpad 3 to 10 days later. The DTH peaked 15 to 18 h after footpad injection and disappeared by 48 h. This specific DTH correlated with the homing of 51Cr-labeled syngeneic bone marrow cells and the infiltration of proliferating cells to the site of antigen administration. Spleen cells from FFP-sensitized mice also gave significant proliferative response to FFP in vitro. The DTH was adoptively transferable by Lyt-1+2-L3T4+ T cells and was H-2 restricted. DTH could be substantially enhanced by pretreatment with cyclophosphamide or pertussigen. Such DTH enhancement was accompanied by concomitant exacerbation of disease progression after L. major infection. Mice injected intravenously with FFP developed substantial immunity to cutaneous leishmaniasis but specifically suppressed DTH reactivity. Treatment of mice with pertussigen before intravenous immunization, however, abolished the protection and reversed the suppression of DTH. These results therefore demonstrate that the early-appearing type of DTH is not involved in host protection but that it actually facilitates disease progression in cutaneous leishmaniasis. Further evidence, which also shows the nonspecific nature of this disease exacerbation, is provided by local cell transfer experiments. Splenic T cells from mice sensitized to keyhole limpet hemocyanin or FFP induced significantly larger lesions compared with normal T cells when they were transferred into the footpad together with specific antigen and L. major promastigotes.

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Selected References

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  1. Arthur R. P., Mason D. T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation. J Exp Med. 1986 Apr 1;163(4):774–786. doi: 10.1084/jem.163.4.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Askenase P. W., Hayden B. J., Gershon R. K. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med. 1975 Mar 1;141(3):697–702. doi: 10.1084/jem.141.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bray R. S., Bryceson A. D. Cutaneous leishmaniasis of the guineapig. Action of sensitised lymphocytes on infected macrophages. Lancet. 1968 Oct 26;2(7574):898–899. doi: 10.1016/s0140-6736(68)91059-3. [DOI] [PubMed] [Google Scholar]
  4. Bryceson A. D., Bray R. S., Dumonde D. C. Experimental cutaneous leishmaniasis. IV. Selective suppression of cell-mediated immunity during the response of guinea-pigs to infection with Leishmania enriettii. Clin Exp Immunol. 1974 Feb;16(2):189–202. [PMC free article] [PubMed] [Google Scholar]
  5. Bryceson A. D. Diffuse cutaneous leishmaniasis in Ethiopia. 3. Immunological studies. IV. Pathogenesis of diffuse cutaneous leishmaniasis. Trans R Soc Trop Med Hyg. 1970;64(3):380–393. doi: 10.1016/0035-9203(70)90174-4. [DOI] [PubMed] [Google Scholar]
  6. Bryceson A. D., Preston P. M., Bray R. S., Dumonde D. C. Experimental cutaneous leishmaniasis. II. Effects of immunosuppression and antigenic competition on the course of infection with Leishmania enriettii in the guinea-pig. Clin Exp Immunol. 1972 Feb;10(2):305–335. [PMC free article] [PubMed] [Google Scholar]
  7. Dhaliwal J. S., Liew F. Y., Cox F. E. Specific suppressor T cells for delayed-type hypersensitivity in susceptible mice immunized against cutaneous leishmaniasis. Infect Immun. 1985 Aug;49(2):417–423. doi: 10.1128/iai.49.2.417-423.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  9. 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]
  10. Howard J. G., Liew F. Y., Hale C., Nicklin S. Prophylactic immunization against experimental leishmaniasis. II. Further characterization of the protective immunity against fatal Leishmania tropica infection induced by irradiated promastigotes. J Immunol. 1984 Jan;132(1):450–455. [PubMed] [Google Scholar]
  11. Liew F. Y., Hale C., Howard J. G. Immunologic regulation of experimental cutaneous leishmaniasis. V. Characterization of effector and specific suppressor T cells. J Immunol. 1982 Apr;128(4):1917–1922. [PubMed] [Google Scholar]
  12. Liew F. Y., Hale C., Howard J. G. Prophylactic immunization against experimental leishmaniasis. IV. Subcutaneous immunization prevents the induction of protective immunity against fatal Leishmania major infection. J Immunol. 1985 Sep;135(3):2095–2101. [PubMed] [Google Scholar]
  13. Liew F. Y., Howard J. G., Hale C. Prophylactic immunization against experimental leishmaniasis. III. Protection against fatal Leishmania tropica infection induced by irradiated promastigotes involves Lyt-1+2- T cells that do not mediate cutaneous DTH. J Immunol. 1984 Jan;132(1):456–461. [PubMed] [Google Scholar]
  14. 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]
  15. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Preston P. M., Dumonde D. C. Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse. Clin Exp Immunol. 1976 Jan;23(1):126–138. [PMC free article] [PubMed] [Google Scholar]
  19. Rezai H. R., Farrell J., Soulsby E. L. Immunological responses of L. donovani infection in mice and significance of T cell in resistance to experimental leishmaniasis. Clin Exp Immunol. 1980 Jun;40(3):508–514. [PMC free article] [PubMed] [Google Scholar]
  20. Sewell W. A., Munoz J. J., Vadas M. A. Enhancement of the intensity, persistence, and passive transfer of delayed-type hypersensitivity lesions by pertussigen in mice. J Exp Med. 1983 Jun 1;157(6):2087–2096. doi: 10.1084/jem.157.6.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shand F. L. Analysis of immunosuppression generated by the graft-versus-host reaction. I. A suppressor T-cell component studied in vivo. Immunology. 1975 Dec;29(6):953–965. [PMC free article] [PubMed] [Google Scholar]
  22. Titus R. G., Lima G. C., Engers H. D., Louis J. A. Exacerbation of murine cutaneous leishmaniasis by adoptive transfer of parasite-specific helper T cell populations capable of mediating Leishmania major-specific delayed-type hypersensitivity. J Immunol. 1984 Sep;133(3):1594–1600. [PubMed] [Google Scholar]
  23. Turk J. L., Bryceson A. D. Immunological phenomena in leprosy and related diseases. Adv Immunol. 1971;13:209–266. doi: 10.1016/s0065-2776(08)60185-6. [DOI] [PubMed] [Google Scholar]

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