Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1989 Mar;75(3):438–443.

Effect of CD4 monoclonal antibody in vivo on lesion development, delayed-type hypersensitivity and interleukin 3 production in experimental murine cutaneous leishmaniasis.

F Y Liew 1, S Millott 1, R Lelchuk 1, S Cobbold 1, H Waldmann 1
PMCID: PMC1541947  PMID: 2784747

Abstract

Highly susceptible BALB/c mice subjected to adult thymectomy followed by prolonged (15 weeks), twice-weekly injections of a low dose (100 micrograms) of CD4 monoclonal antibody (MoAb) develop resistance to otherwise uniformly fatal and disseminating Leishmania major infection. In contrast, similar treatment with CD8 MoAb has no effect on the course of L. major infection. CD4 MoAb administered after the lesion establishment also has no effect. Mice which become resistant following CD4 MoAb treatment developed the classical delayed-type hypersensitivity (DTH) which persisted at 72 h after footpad injection with killed L. major promastigotes. A substantial degree of resistance can also be induced in the BALB/c mice with two i.v. high doses of 500 micrograms of CD4 MoAb given immediately prior to L. major infection. The treated mice developed classical DTH and significantly smaller lesions. The spleen cells from these mice also produced significantly lower levels of IL-3 compared to that of untreated control mice when cultured with L. major antigens in vitro. In contrast, genetically resistant CBA mice treated with CD4 MoAb developed significantly larger lesions but lower levels of classical DTH compared to untreated mice. These data confirmed and extended earlier reports on the prophylactic effect of CD4 MoAb in susceptible BALB/c mice and the disease exacerbative effect in the resistant CBA mice. The data also further illustrate the direct correlation between classical DTH and resistance, and the inverse correlation between IL-3 production and resistance in experimental cutaneous leishmaniasis.

Full text

PDF
438

Selected References

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

  1. Behforouz N. C., Wenger C. D., Mathison B. A. Prophylactic treatment of BALB/c mice with cyclosporine A and its analog B-5-49 enhances resistance to Leishmania major. J Immunol. 1986 Apr 15;136(8):3067–3075. [PubMed] [Google Scholar]
  2. Cobbold S. P., Jayasuriya A., Nash A., Prospero T. D., Waldmann H. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature. 1984 Dec 6;312(5994):548–551. doi: 10.1038/312548a0. [DOI] [PubMed] [Google Scholar]
  3. De Rossell R. A., Bray R. S., Alexander J. The correlation between delayed hypersensitivity, lymphocyte activation and protective immunity in experimental murine leishmaniasis. Parasite Immunol. 1987 Jan;9(1):105–115. doi: 10.1111/j.1365-3024.1987.tb00492.x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Handman E., Mitchell G. F. Immunization with Leishmania receptor for macrophages protects mice against cutaneous leishmaniasis. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5910–5914. doi: 10.1073/pnas.82.17.5910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Howard J. G., Hale C., Liew F. Y. 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. J Exp Med. 1981 Mar 1;153(3):557–568. doi: 10.1084/jem.153.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Howard J. G., Nicklin S., Hale C., Liew F. Y. Prophylactic immunization against experimental leishmaniasis: I. Protection induced in mice genetically vulnerable to fatal Leishmania tropica infection. J Immunol. 1982 Nov;129(5):2206–2212. [PubMed] [Google Scholar]
  9. Lelchuk R., Graveley R., Liew F. Y. Susceptibility to murine cutaneous leishmaniasis correlates with the capacity to generate interleukin 3 in response to leishmania antigen in vitro. Cell Immunol. 1988 Jan;111(1):66–76. doi: 10.1016/0008-8749(88)90051-2. [DOI] [PubMed] [Google Scholar]
  10. Liew F. Y. Cell-mediated immunity in experimental cutaneous Leishmaniasis. Parasitol Today. 1986 Oct;2(10):264–270. doi: 10.1016/0169-4758(86)90135-3. [DOI] [PubMed] [Google Scholar]
  11. Liew F. Y., Dhaliwal J. S. Distinctive cellular immunity in genetically susceptible BALB/c mice recovered from Leishmania major infection or after subcutaneous immunization with killed parasites. J Immunol. 1987 Jun 15;138(12):4450–4456. [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. Liew F. Y. Specific suppression of responses to Leishmania tropica by a cloned T-cell line. Nature. 1983 Oct 13;305(5935):630–632. doi: 10.1038/305630a0. [DOI] [PubMed] [Google Scholar]
  15. Milon G., Titus R. G., Cerottini J. C., Marchal G., Louis J. A. Higher frequency of Leishmania major-specific L3T4+ T cells in susceptible BALB/c as compared with resistant CBA mice. J Immunol. 1986 Feb 15;136(4):1467–1471. [PubMed] [Google Scholar]
  16. 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]
  17. Russell D. G., Alexander J. Effective immunization against cutaneous leishmaniasis with defined membrane antigens reconstituted into liposomes. J Immunol. 1988 Feb 15;140(4):1274–1279. [PubMed] [Google Scholar]
  18. Sacks D. L., Scott P. A., Asofsky R., Sher F. A. Cutaneous leishmaniasis in anti-IgM-treated mice: enhanced resistance due to functional depletion of a B cell-dependent T cell involved in the suppressor pathway. J Immunol. 1984 Apr;132(4):2072–2077. [PubMed] [Google Scholar]
  19. Sadick M. D., Heinzel F. P., Shigekane V. M., Fisher W. L., Locksley R. M. Cellular and humoral immunity to Leishmania major in genetically susceptible mice after in vivo depletion of L3T4+ T cells. J Immunol. 1987 Aug 15;139(4):1303–1309. [PubMed] [Google Scholar]
  20. Scott P., Natovitz P., Sher A. B lymphocytes are required for the generation of T cells that mediate healing of cutaneous leishmaniasis. J Immunol. 1986 Aug 1;137(3):1017–1021. [PubMed] [Google Scholar]
  21. Solbach W., Forberg K., Kammerer E., Bogdan C., Röllinghoff M. Suppressive effect of cyclosporin A on the development of Leishmania tropica-induced lesions in genetically susceptible BALB/c mice. J Immunol. 1986 Jul 15;137(2):702–707. [PubMed] [Google Scholar]
  22. Titus R. G., Ceredig R., Cerottini J. C., Louis J. A. Therapeutic effect of anti-L3T4 monoclonal antibody GK1.5 on cutaneous leishmaniasis in genetically-susceptible BALB/c mice. J Immunol. 1985 Sep;135(3):2108–2114. [PubMed] [Google Scholar]
  23. 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]
  24. Titus R. G., Milon G., Marchal G., Vassalli P., Cerottini J. C., Louis J. A. Involvement of specific Lyt-2+ T cells in the immunological control of experimentally induced murine cutaneous leishmaniasis. Eur J Immunol. 1987 Oct;17(10):1429–1433. doi: 10.1002/eji.1830171007. [DOI] [PubMed] [Google Scholar]
  25. 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]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES