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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Jun;96(3):410–415. doi: 10.1111/j.1365-2249.1994.tb06043.x

Dichotomy of the human T cell response to Leishmania antigens. I. Th1-like response to Leishmania major promastigote antigens in individuals recovered from cutaneous leishmaniasis.

M Kemp 1, A S Hey 1, J A Kurtzhals 1, C B Christensen 1, A Gaafar 1, M D Mustafa 1, A A Kordofani 1, A Ismail 1, A Kharazmi 1, T G Theander 1
PMCID: PMC1534571  PMID: 8004809

Abstract

The T cell response to antigens from Leishmania major promastigotes was investigated in peripheral blood mononuclear cells from Sudanese individuals with a history of cutaneous leishmaniasis (CL), Sudanese individuals with positive DTH reaction in the leishmanin skin test but with no history of skin lesions, and in Danes without known exposure to Leishmania parasites. Proliferation and production of interferon-gamma (IFN-gamma) and IL-4 in antigen-stimulated cultures was measured. Lymphocytes from individuals with a history of CL proliferated vigorously and produced IFN-gamma after stimulation with either a crude preparation of L. major antigens or the major surface protease gp63. These cultures produced no or only little IL-4. Also cells from leishmanin skin test-positive donors with no history of CL produced IFN-gamma and no IL-4 in response to L. major antigens. Cells from the unexposed Danes were not activated by gp63. The cells from Danish donors produced either IFN-gamma or IL-4, but not both cytokines after incubation with the crude preparation of L. major antigens. The data show that the T cell response to Leishmania antigens in humans who have had uncomplicated CL or subclinical L. major infection is an IFN-gamma-producing Th1-like response.

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Selected References

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  1. Akuffo H. O., Britton S. F. Contribution of non-Leishmania-specific immunity to resistance to Leishmania infection in humans. Clin Exp Immunol. 1992 Jan;87(1):58–64. doi: 10.1111/j.1365-2249.1992.tb06413.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bogdan C., Stenger S., Röllinghoff M., Solbach W. Cytokine interactions in experimental cutaneous leishmaniasis. Interleukin 4 synergizes with interferon-gamma to activate murine macrophages for killing of Leishmania major amastigotes. Eur J Immunol. 1991 Feb;21(2):327–333. doi: 10.1002/eji.1830210213. [DOI] [PubMed] [Google Scholar]
  3. Bouvier J., Etges R. J., Bordier C. Identification and purification of membrane and soluble forms of the major surface protein of Leishmania promastigotes. J Biol Chem. 1985 Dec 15;260(29):15504–15509. [PubMed] [Google Scholar]
  4. Carvalho E. M., Barral A., Pedral-Sampaio D., Barral-Netto M., Badaró R., Rocha H., Johnson W. D., Jr Immunologic markers of clinical evolution in children recently infected with Leishmania donovani chagasi. J Infect Dis. 1992 Mar;165(3):535–540. doi: 10.1093/infdis/165.3.535. [DOI] [PubMed] [Google Scholar]
  5. Douvas G. S., Looker D. L., Vatter A. E., Crowle A. J. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria. Infect Immun. 1985 Oct;50(1):1–8. doi: 10.1128/iai.50.1.1-8.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans T. G., Teixeira M. J., McAuliffe I. T., Vasconcelos I., Vasconcelos A. W., Sousa A. de A., Lima J. W., Pearson R. D. Epidemiology of visceral leishmaniasis in northeast Brazil. J Infect Dis. 1992 Nov;166(5):1124–1132. doi: 10.1093/infdis/166.5.1124. [DOI] [PubMed] [Google Scholar]
  7. Harms G., Zwingenberger K., Chéhadé A. K., Talhari S., Racz P., Mouakeh A., Douba M., Näkel L., Naiff R. D., Kremsner P. G. Effects of intradermal gamma-interferon in cutaneous leishmaniasis. Lancet. 1989 Jun 10;1(8650):1287–1292. doi: 10.1016/s0140-6736(89)92686-x. [DOI] [PubMed] [Google Scholar]
  8. Hoover D. L., Nacy C. A., Meltzer M. S. Human monocyte activation for cytotoxicity against intracellular Leishmania donovani amastigotes: induction of microbicidal activity by interferon-gamma. Cell Immunol. 1985 Sep;94(2):500–511. doi: 10.1016/0008-8749(85)90274-6. [DOI] [PubMed] [Google Scholar]
  9. Hviid L., Albeck G., Hansen B., Theander T. G., Talbot A. A new portable device for automatic controlled-gradient cryopreservation of blood mononuclear cells. J Immunol Methods. 1993 Jan 4;157(1-2):135–142. doi: 10.1016/0022-1759(93)90079-m. [DOI] [PubMed] [Google Scholar]
  10. Jaffe C. L., Shor R., Trau H., Passwell J. H. Parasite antigens recognized by patients with cutaneous leishmaniasis. Clin Exp Immunol. 1990 Apr;80(1):77–82. doi: 10.1111/j.1365-2249.1990.tb06444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kadaro A. Y., Ghalib H. W., Ali M. S., Eltoum I., Ismail A., Gaafar A., Kemp M., Kordofani A. A., Reed S. G., el-Hassan A. M. Prevalence of cutaneous leishmaniasis along the Nile River north of Khartoum (Sudan) in the aftermath of an epidemic in 1985. Am J Trop Med Hyg. 1993 Jan;48(1):44–49. doi: 10.4269/ajtmh.1993.48.44. [DOI] [PubMed] [Google Scholar]
  12. Kemp M., Hansen M. B., Theander T. G. Recognition of Leishmania antigens by T lymphocytes from nonexposed individuals. Infect Immun. 1992 Jun;60(6):2246–2251. doi: 10.1128/iai.60.6.2246-2251.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kemp M., Kurtzhals J. A., Bendtzen K., Poulsen L. K., Hansen M. B., Koech D. K., Kharazmi A., Theander T. G. Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis. Infect Immun. 1993 Mar;61(3):1069–1073. doi: 10.1128/iai.61.3.1069-1073.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kemp M., Theander T. G., Handman E., Hey A. S., Kurtzhals J. A., Hviid L., Sørensen A. L., Were J. O., Koech D. K., Kharazmi A. Activation of human T lymphocytes by Leishmania lipophosphoglycan. Scand J Immunol. 1991 Feb;33(2):219–224. doi: 10.1111/j.1365-3083.1991.tb03752.x. [DOI] [PubMed] [Google Scholar]
  15. Kurtzhals J. A., Hansen M. B., Hey A. S., Poulsen L. K. Measurement of antigen-dependent interleukin-4 production by human peripheral blood mononuclear cells. Introduction of an amplification step using ionomycin and phorbol myristate acetate. J Immunol Methods. 1992 Dec 8;156(2):239–245. doi: 10.1016/0022-1759(92)90031-n. [DOI] [PubMed] [Google Scholar]
  16. Kurtzhals J. A., Hey A. S., Jardim A., Kemp M., Schaefer K. U., Odera E. O., Christensen C. B., Githure J. I., Olafson R. W., Theander T. G. Dichotomy of the human T cell response to Leishmania antigens. II. Absent or Th2-like response to gp63 and Th1-like response to lipophosphoglycan-associated protein in cells from cured visceral leishmaniasis patients. Clin Exp Immunol. 1994 Jun;96(3):416–421. doi: 10.1111/j.1365-2249.1994.tb06044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kurtzhals J. A., Hey A. S., Theander T. G., Odera E., Christensen C. B., Githure J. I., Koech D. K., Schaefer K. U., Handman E., Kharazmi A. Cellular and humoral immune responses in a population from the Baringo District, Kenya to Leishmania promastigote lipophosphoglycan. Am J Trop Med Hyg. 1992 Apr;46(4):480–488. doi: 10.4269/ajtmh.1992.46.480. [DOI] [PubMed] [Google Scholar]
  18. Lehn M., Weiser W. Y., Engelhorn S., Gillis S., Remold H. G. IL-4 inhibits H2O2 production and antileishmanial capacity of human cultured monocytes mediated by IFN-gamma. J Immunol. 1989 Nov 1;143(9):3020–3024. [PubMed] [Google Scholar]
  19. Liew F. Y., Millott S., Li Y., Lelchuk R., Chan W. L., Ziltener H. Macrophage activation by interferon-gamma from host-protective T cells is inhibited by interleukin (IL)3 and IL4 produced by disease-promoting T cells in leishmaniasis. Eur J Immunol. 1989 Jul;19(7):1227–1232. doi: 10.1002/eji.1830190712. [DOI] [PubMed] [Google Scholar]
  20. Meller-Melloul C., Farnarier C., Dunan S., Faugere B., Franck J., Mary C., Bongrand P., Quilici M., Kaplanski S. Evidence of subjects sensitized to Leishmania infantum on the French Mediterranean coast: differences in gamma interferon production between this population and visceral leishmaniasis patients. Parasite Immunol. 1991 Sep;13(5):531–536. doi: 10.1111/j.1365-3024.1991.tb00549.x. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Murray H. W., Rubin B. Y., Rothermel C. D. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest. 1983 Oct;72(4):1506–1510. doi: 10.1172/JCI111107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nacy C. A., Fortier A. H., Meltzer M. S., Buchmeier N. A., Schreiber R. D. Macrophage activation to kill Leishmania major: activation of macrophages for intracellular destruction of amastigotes can be induced by both recombinant interferon-gamma and non-interferon lymphokines. J Immunol. 1985 Nov;135(5):3505–3511. [PubMed] [Google Scholar]
  24. Pampiglione S., Manson-Bahr P. E., Giungi F., Giunti G., Parenti A., Canestri Trotti G. Studies on Mediterranean leishmaniasis. 2. Asymptomatic cases of visceral leishmaniasis. Trans R Soc Trop Med Hyg. 1974;68(6):447–453. doi: 10.1016/0035-9203(74)90067-4. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Russo D. M., Burns J. M., Jr, Carvalho E. M., Armitage R. J., Grabstein K. H., Button L. L., McMaster W. R., Reed S. G. Human T cell responses to gp63, a surface antigen of Leishmania. J Immunol. 1991 Nov 15;147(10):3575–3580. [PubMed] [Google Scholar]
  27. Sacks D. L., Lal S. L., Shrivastava S. N., Blackwell J., Neva F. A. An analysis of T cell responsiveness in Indian kala-azar. J Immunol. 1987 Feb 1;138(3):908–913. [PubMed] [Google Scholar]
  28. Scott P., Pearce E., Cheever A. W., Coffman R. L., Sher A. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol Rev. 1989 Dec;112:161–182. doi: 10.1111/j.1600-065x.1989.tb00557.x. [DOI] [PubMed] [Google Scholar]
  29. Wyler D. J., Weinbaum F. I., Herrod H. R. Characterization of in vitro proliferative responses of human lymphocytes to leishmanial antigens. J Infect Dis. 1979 Aug;140(2):215–221. doi: 10.1093/infdis/140.2.215. [DOI] [PubMed] [Google Scholar]
  30. el-Safi S. H., Peters W. Studies on the leishmaniases in the Sudan. 1. Epidemic of cutaneous leishmaniasis in Khartoum. Trans R Soc Trop Med Hyg. 1991 Jan-Feb;85(1):44–47. doi: 10.1016/0035-9203(91)90151-n. [DOI] [PubMed] [Google Scholar]

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