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. 1989 Jun;83(6):1868–1875. doi: 10.1172/JCI114093

Profile of human T cell response to leishmanial antigens. Analysis by immunoblotting.

P C Melby 1, F A Neva 1, D L Sacks 1
PMCID: PMC303907  PMID: 2470787

Abstract

Control and resolution of leishmanial infection depends primarily on T cell-mediated immune mechanisms. The nature of the leishmanial antigens involved in eliciting T cell immunity is unknown. We have examined the pattern of peripheral blood lymphocyte responses in patients with active, healed, or subclinical leishmanial infection to fractionated leishmanial antigens using a T cell immunoblotting method in which nitrocellulose-bound leishmanial antigen, resolved by one or two dimensional electrophoresis, are incorporated into lymphocyte cultures. The proliferative and IFN-gamma responses of cells from patients with healed mucosal or cutaneous leishmaniasis were remarkably heterogeneous and occurred to as many as 50-70 distinct antigens. In contrast, responses from subjects with active, nonhealing, diffuse cutaneous leishmaniasis were either absent or present to only a small number of antigens. Control and resolution of leishmaniasis, and resistance to reinfection, is therefore associated with a T cell response to a large and diverse pool of parasite antigens. The method of T cell immunoblotting appears to offer a powerful, rapid, and relatively simple approach to the identification of antigens involved in eliciting a T cell response in human leishmaniasis.

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Selected References

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  1. Badaró R., Jones T. C., Lorenço R., Cerf B. J., Sampaio D., Carvalho E. M., Rocha H., Teixeira R., Johnson W. D., Jr A prospective study of visceral leishmaniasis in an endemic area of Brazil. J Infect Dis. 1986 Oct;154(4):639–649. doi: 10.1093/infdis/154.4.639. [DOI] [PubMed] [Google Scholar]
  2. Berzofsky J. A., Richman L. K., Killion D. J. Distinct H-2-linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4046–4050. doi: 10.1073/pnas.76.8.4046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bryceson A. D. Diffuse cutaneous leishmaniasis in Ethiopia. I. The clinical and histological features of the disease. Trans R Soc Trop Med Hyg. 1969;63(6):708–737. doi: 10.1016/0035-9203(69)90116-3. [DOI] [PubMed] [Google Scholar]
  5. Carvalho E. M., Badaró R., Reed S. G., Jones T. C., Johnson W. D., Jr Absence of gamma interferon and interleukin 2 production during active visceral leishmaniasis. J Clin Invest. 1985 Dec;76(6):2066–2069. doi: 10.1172/JCI112209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carvalho E. M., Johnson W. D., Barreto E., Marsden P. D., Costa J. L., Reed S., Rocha H. Cell mediated immunity in American cutaneous and mucosal leishmaniasis. J Immunol. 1985 Dec;135(6):4144–4148. [PubMed] [Google Scholar]
  7. Carvalho E. M., Teixeira R. S., Johnson W. D., Jr Cell-mediated immunity in American visceral leishmaniasis: reversible immunosuppression during acute infection. Infect Immun. 1981 Aug;33(2):498–500. doi: 10.1128/iai.33.2.498-500.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Castés M., Agnelli A., Rondón A. J. Mechanisms associated with immunoregulation in human American cutaneous leishmaniasis. Clin Exp Immunol. 1984 Aug;57(2):279–286. [PMC free article] [PubMed] [Google Scholar]
  9. Chang K. P., Chiao J. W. Cellular immunity of mice to Leishmania donovani in vitro: lymphokine-mediated killing of intracellular parasites in macrophages. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7083–7087. doi: 10.1073/pnas.78.11.7083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Convit J., Pinardi M. E., Rondón A. J. Diffuse cutaneous leishmaniasis: a disease due to an immunological defect of the host. Trans R Soc Trop Med Hyg. 1972;66(4):603–610. doi: 10.1016/0035-9203(72)90306-9. [DOI] [PubMed] [Google Scholar]
  11. Curry R. C., Kiener P. A., Spitalny G. L. A sensitive immunochemical assay for biologically active MuIFN-gamma. J Immunol Methods. 1987 Nov 23;104(1-2):137–142. doi: 10.1016/0022-1759(87)90497-2. [DOI] [PubMed] [Google Scholar]
  12. Guirges S. Y. Natural and experimental re-infection of man with Oriental sore. Ann Trop Med Parasitol. 1971 Jun;65(2):197–205. doi: 10.1080/00034983.1971.11686746. [DOI] [PubMed] [Google Scholar]
  13. Haldar J. P., Ghose S., Saha K. C., Ghose A. C. Cell-mediated immune response in Indian kala-azar and post-kala-azar dermal leishmaniasis. Infect Immun. 1983 Nov;42(2):702–707. doi: 10.1128/iai.42.2.702-707.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Ho M., Koech D. K., Iha D. W., Bryceson A. D. Immunosuppression in Kenyan visceral leishmaniasis. Clin Exp Immunol. 1983 Feb;51(2):207–214. [PMC free article] [PubMed] [Google Scholar]
  16. Ho M., Siongok T. K., Lyerly W. H., Smith D. H. Prevalence and disease spectrum in a new focus of visceral leishmaniasis in Kenya. Trans R Soc Trop Med Hyg. 1982;76(6):741–746. doi: 10.1016/0035-9203(82)90095-5. [DOI] [PubMed] [Google Scholar]
  17. Hochstrasser D. F., Harrington M. G., Hochstrasser A. C., Miller M. J., Merril C. R. Methods for increasing the resolution of two-dimensional protein electrophoresis. Anal Biochem. 1988 Sep;173(2):424–435. doi: 10.1016/0003-2697(88)90209-6. [DOI] [PubMed] [Google Scholar]
  18. Howard J. G. Immunological regulation and control of experimental leishmaniasis. Int Rev Exp Pathol. 1986;28:79–116. [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Lamb J. R., Green N. Analysis of the antigen specificity of influenza haemagglutinin-immune human T lymphocyte clones: identification of an immunodominant region for T cells. Immunology. 1983 Dec;50(4):659–666. [PMC free article] [PubMed] [Google Scholar]
  21. Lamb J. R., Young D. B. A novel approach to the identification of T-cell epitopes in Mycobacterium tuberculosis using human T-lymphocyte clones. Immunology. 1987 Jan;60(1):1–5. [PMC free article] [PubMed] [Google Scholar]
  22. MANSON-BAHR P. E. Immunity in kala-azar. Trans R Soc Trop Med Hyg. 1961 Nov;55:550–555. doi: 10.1016/0035-9203(61)90078-5. [DOI] [PubMed] [Google Scholar]
  23. Marsden P. D. Mucosal leishmaniasis ("espundia" Escomel, 1911). Trans R Soc Trop Med Hyg. 1986;80(6):859–876. doi: 10.1016/0035-9203(86)90243-9. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Murray H. W., Masur H., Keithly J. S. Cell-mediated immune response in experimental visceral leishmaniasis. I. Correlation between resistance to Leishmania donovani and lymphokine-generating capacity. J Immunol. 1982 Jul;129(1):344–350. [PubMed] [Google Scholar]
  26. Nacy C. A., Meltzer M. S., Leonard E. J., Wyler D. J. Intracellular replication and lymphokine-induced destruction of Leishmania tropica in C3H/HeN mouse macrophages. J Immunol. 1981 Dec;127(6):2381–2386. [PubMed] [Google Scholar]
  27. Oakley B. R., Kirsch D. R., Morris N. R. A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels. Anal Biochem. 1980 Jul 1;105(2):361–363. doi: 10.1016/0003-2697(80)90470-4. [DOI] [PubMed] [Google Scholar]
  28. Pearson R. D., Wheeler D. A., Harrison L. H., Kay H. D. The immunobiology of leishmaniasis. Rev Infect Dis. 1983 Sep-Oct;5(5):907–927. doi: 10.1093/clinids/5.5.907. [DOI] [PubMed] [Google Scholar]
  29. Rezai H. R., Ardehali S. M., Amirhakimi G., Kharazmi A. Immunological features of kala-azar. Am J Trop Med Hyg. 1978 Nov;27(6):1079–1083. doi: 10.4269/ajtmh.1978.27.1079. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Schurr E., Kidane K., Yemaneberhan T., Wunderlich F. Cutaneous leishmaniasis in Ethiopia: I. Lymphocyte transformation and antibody titre. Trop Med Parasitol. 1986 Dec;37(4):403–408. [PubMed] [Google Scholar]
  32. Scott P., Pearce E., Natovitz P., Sher A. Vaccination against cutaneous leishmaniasis in a murine model. I. Induction of protective immunity with a soluble extract of promastigotes. J Immunol. 1987 Jul 1;139(1):221–227. [PubMed] [Google Scholar]
  33. Scott P., Pearce E., Natovitz P., Sher A. Vaccination against cutaneous leishmaniasis in a murine model. II. Immunologic properties of protective and nonprotective subfractions of soluble promastigote extract. J Immunol. 1987 Nov 1;139(9):3118–3125. [PubMed] [Google Scholar]
  34. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Young D. B., Lamb J. R. T lymphocytes respond to solid-phase antigen: a novel approach to the molecular analysis of cellular immunity. Immunology. 1986 Oct;59(2):167–171. [PMC free article] [PubMed] [Google Scholar]

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