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. 1996 Jan;64(1):215–221. doi: 10.1128/iai.64.1.215-221.1996

Chagas' disease is attenuated in mice lacking gamma delta T cells.

E C Santos Lima 1, P Minoprio 1
PMCID: PMC173748  PMID: 8557342

Abstract

The role of gamma delta T cells in the immunopathology of Chagas' disease is evaluated by monitoring the course of Trypanosoma cruzi infection in mice lacking gamma delta T cells after disruption of the T-cell receptor C delta locus. Levels of parasitemia, states of lymphocyte activation, and levels of lymphokine production as well as tissue pathology are compared in delta knockout mice and their littermates in acute and chronic phases of infection. Although the levels of circulating parasites do not significantly differ in the two groups, mortality scores and numbers of inflammatory lesions of skeletal and cardiac muscles are lower in gamma delta T cell-deficient m ice than in littermate controls. Furthermore, polyclonal lymphocyte activation, as measured by proliferative activities and numbers of B- and T-cell blasts in the spleen, are reduced in deficient mice in the acute and chronic phases of infection. Levels of gamma interferon mRNA obtained from total spleen cells, known to be a critical lymphokine in resistance to T. cruzi infection, are significantly higher in uninfected gamma delta T cell-deficient mice than in control animals and slightly above levels for littermates in the course of acute infection. Interestingly, however, in chronic phases, the levels of this lymphokine are not statistically different between the two groups of mice. These results indicate that gamma delta T cells do not play a crucial role in parasite clearance during the acute phase of the disease but contribute to the mechanisms leading to tissue damage and pathology.

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Selected References

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  1. Andrade Z. A. Mechanisms of myocardial damage in Trypanosoma cruzi infection. Ciba Found Symp. 1983;99:214–233. doi: 10.1002/9780470720806.ch12. [DOI] [PubMed] [Google Scholar]
  2. Cardillo F., Falcão R. P., Rossi M. A., Mengel J. An age-related gamma delta T cell suppressor activity correlates with the outcome of autoimmunity in experimental Trypanosoma cruzi infection. Eur J Immunol. 1993 Oct;23(10):2597–2605. doi: 10.1002/eji.1830231033. [DOI] [PubMed] [Google Scholar]
  3. D'Imperio Lima M. R., Joskowicz M., Coutinho A., Kipnis T., Eisen H. Very large and isotypically atypical polyclonal plaque-forming cell responses in mice infected with Trypanosoma cruzi. Eur J Immunol. 1985 Feb;15(2):201–203. doi: 10.1002/eji.1830150219. [DOI] [PubMed] [Google Scholar]
  4. Ferrick D. A., Schrenzel M. D., Mulvania T., Hsieh B., Ferlin W. G., Lepper H. Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature. 1995 Jan 19;373(6511):255–257. doi: 10.1038/373255a0. [DOI] [PubMed] [Google Scholar]
  5. Fu Y. X., Roark C. E., Kelly K., Drevets D., Campbell P., O'Brien R., Born W. Immune protection and control of inflammatory tissue necrosis by gamma delta T cells. J Immunol. 1994 Oct 1;153(7):3101–3115. [PubMed] [Google Scholar]
  6. Haas W., Pereira P., Tonegawa S. Gamma/delta cells. Annu Rev Immunol. 1993;11:637–685. doi: 10.1146/annurev.iy.11.040193.003225. [DOI] [PubMed] [Google Scholar]
  7. Hardy R. R., Hayakawa K., Shimizu M., Yamasaki K., Kishimoto T. Rheumatoid factor secretion from human Leu-1+ B cells. Science. 1987 Apr 3;236(4797):81–83. doi: 10.1126/science.3105057. [DOI] [PubMed] [Google Scholar]
  8. Hayakawa K., Hardy R. R., Honda M., Herzenberg L. A., Steinberg A. D., Herzenberg L. A. Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2494–2498. doi: 10.1073/pnas.81.8.2494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hayakawa K., Hardy R. R. Normal, autoimmune, and malignant CD5+ B cells: the Ly-1 B lineage? Annu Rev Immunol. 1988;6:197–218. doi: 10.1146/annurev.iy.06.040188.001213. [DOI] [PubMed] [Google Scholar]
  10. Hiromatsu K., Yoshikai Y., Matsuzaki G., Ohga S., Muramori K., Matsumoto K., Bluestone J. A., Nomoto K. A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice. J Exp Med. 1992 Jan 1;175(1):49–56. doi: 10.1084/jem.175.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hohlfeld R., Engel A. G. The role of gamma-delta T lymphocytes in inflammatory muscle disease. Chem Immunol. 1992;53:75–85. [PubMed] [Google Scholar]
  12. Hontebeyrie-Joskowicz M., Said G., Milon G., Marchal G., Eisen H. L3T4+ T cells able to mediate parasite-specific delayed-type hypersensitivity play a role in the pathology of experimental Chagas' disease. Eur J Immunol. 1987 Jul;17(7):1027–1033. doi: 10.1002/eji.1830170720. [DOI] [PubMed] [Google Scholar]
  13. Itohara S., Mombaerts P., Lafaille J., Iacomini J., Nelson A., Clarke A. R., Hooper M. L., Farr A., Tonegawa S. T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes. Cell. 1993 Feb 12;72(3):337–348. doi: 10.1016/0092-8674(93)90112-4. [DOI] [PubMed] [Google Scholar]
  14. Itohara S., Nakanishi N., Kanagawa O., Kubo R., Tonegawa S. Monoclonal antibodies specific to native murine T-cell receptor gamma delta: analysis of gamma delta T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5094–5098. doi: 10.1073/pnas.86.13.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  16. Lang F. P., Pollock B. H., Riley W. J., Maclaren N. K., Barrett D. J. The temporal association between gamma delta T cells and the natural history of insulin-dependent diabetes. J Autoimmun. 1993 Feb;6(1):107–119. doi: 10.1006/jaut.1993.1009. [DOI] [PubMed] [Google Scholar]
  17. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marcos M. A., Toribio M. L., de la Hera A., Márquez C., Gaspar M. L., Martínez C. Mutual cell interactions and the selection of immune repertoires: implication in autoimmunity. Immunol Today. 1988 Jul-Aug;9(7-8):204–207. doi: 10.1016/0167-5699(88)91214-5. [DOI] [PubMed] [Google Scholar]
  19. Minoprio P. M., Coutinho A., Joskowicz M., D'Imperio Lima M. R., Eisen H. Polyclonal lymphocyte responses to murine Trypanosoma cruzi infection. II. Cytotoxic T lymphocytes. Scand J Immunol. 1986 Dec;24(6):669–679. doi: 10.1111/j.1365-3083.1986.tb02186.x. [DOI] [PubMed] [Google Scholar]
  20. Minoprio P. M., Eisen H., Forni L., D'Imperio Lima M. R., Joskowicz M., Coutinho A. Polyclonal lymphocyte responses to murine Trypanosoma cruzi infection. I. Quantitation of both T- and B-cell responses. Scand J Immunol. 1986 Dec;24(6):661–668. doi: 10.1111/j.1365-3083.1986.tb02185.x. [DOI] [PubMed] [Google Scholar]
  21. Minoprio P., Bandeira A., Pereira P., Mota Santos T., Coutinho A. Preferential expansion of Ly-1 B and CD4- CD8- T cells in the polyclonal lymphocyte responses to murine T. cruzi infection. Int Immunol. 1989;1(2):176–184. doi: 10.1093/intimm/1.2.176. [DOI] [PubMed] [Google Scholar]
  22. Minoprio P., Burlen O., Pereira P., Guilbert B., Andrade L., Hontebeyrie-Joskowicz M., Coutinho A. Most B cells in acute Trypanosoma cruzi infection lack parasite specificity. Scand J Immunol. 1988 Nov;28(5):553–561. doi: 10.1111/j.1365-3083.1988.tb01487.x. [DOI] [PubMed] [Google Scholar]
  23. Minoprio P., Eisen H., Joskowicz M., Pereira P., Coutinho A. Suppression of polyclonal antibody production in Trypanosoma cruzi-infected mice by treatment with anti-L3T4 antibodies. J Immunol. 1987 Jul 15;139(2):545–550. [PubMed] [Google Scholar]
  24. Minoprio P., Itohara S., Heusser C., Tonegawa S., Coutinho A. Immunobiology of murine T. cruzi infection: the predominance of parasite-nonspecific responses and the activation of TCRI T cells. Immunol Rev. 1989 Dec;112:183–207. doi: 10.1111/j.1600-065x.1989.tb00558.x. [DOI] [PubMed] [Google Scholar]
  25. Minoprio P., el Cheikh M. C., Murphy E., Hontebeyrie-Joskowicz M., Coffman R., Coutinho A., O'Garra A. Xid-associated resistance to experimental Chagas' disease is IFN-gamma dependent. J Immunol. 1993 Oct 15;151(8):4200–4208. [PubMed] [Google Scholar]
  26. Mombaerts P., Arnoldi J., Russ F., Tonegawa S., Kaufmann S. H. Different roles of alpha beta and gamma delta T cells in immunity against an intracellular bacterial pathogen. Nature. 1993 Sep 2;365(6441):53–56. doi: 10.1038/365053a0. [DOI] [PubMed] [Google Scholar]
  27. Mosmann T. R., Schumacher J. H., Street N. F., Budd R., O'Garra A., Fong T. A., Bond M. W., Moore K. W., Sher A., Fiorentino D. F. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev. 1991 Oct;123:209–229. doi: 10.1111/j.1600-065x.1991.tb00612.x. [DOI] [PubMed] [Google Scholar]
  28. Murphy E., Hieny S., Sher A., O'Garra A. Detection of in vivo expression of interleukin-10 using a semi-quantitative polymerase chain reaction method in Schistosoma mansoni infected mice. J Immunol Methods. 1993 Jun 18;162(2):211–223. doi: 10.1016/0022-1759(93)90386-l. [DOI] [PubMed] [Google Scholar]
  29. Plata F., Garcia-Pons F., Wietzerbin J. Immune resistance to Trypanosoma cruzi: synergy of specific antibodies and recombinant interferon gamma in vivo. Ann Inst Pasteur Immunol. 1987 May-Jun;138(3):397–415. doi: 10.1016/s0769-2625(87)80051-x. [DOI] [PubMed] [Google Scholar]
  30. Reed S. G., Brownell C. E., Russo D. M., Silva J. S., Grabstein K. H., Morrissey P. J. IL-10 mediates susceptibility to Trypanosoma cruzi infection. J Immunol. 1994 Oct 1;153(7):3135–3140. [PubMed] [Google Scholar]
  31. Reed S. G. In vivo administration of recombinant IFN-gamma induces macrophage activation, and prevents acute disease, immune suppression, and death in experimental Trypanosoma cruzi infections. J Immunol. 1988 Jun 15;140(12):4342–4347. [PubMed] [Google Scholar]
  32. Reis D. D., Jones E. M., Tostes S., Jr, Lopes E. R., Gazzinelli G., Colley D. G., McCurley T. L. Characterization of inflammatory infiltrates in chronic chagasic myocardial lesions: presence of tumor necrosis factor-alpha+ cells and dominance of granzyme A+, CD8+ lymphocytes. Am J Trop Med Hyg. 1993 May;48(5):637–644. doi: 10.4269/ajtmh.1993.48.637. [DOI] [PubMed] [Google Scholar]
  33. Rosat J. P., MacDonald H. R., Louis J. A. A role for gamma delta + T cells during experimental infection of mice with Leishmania major. J Immunol. 1993 Jan 15;150(2):550–555. [PubMed] [Google Scholar]
  34. Russo N., Starobinas N. Macrophage activation and resistance to Trypanosoma cruzi infection. Res Immunol. 1991 Feb;142(2):144–146. doi: 10.1016/0923-2494(91)90026-f. [DOI] [PubMed] [Google Scholar]
  35. Sato M. N., Yamashiro-Kanashiro E. H., Tanji M. M., Kaneno R., Higuchi M. L., Duarte A. J. CD8+ cells and natural cytotoxic activity among spleen, blood, and heart lymphocytes during the acute phase of Trypanosoma cruzi infection in rats. Infect Immun. 1992 Mar;60(3):1024–1030. doi: 10.1128/iai.60.3.1024-1030.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sher A., Coffman R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol. 1992;10:385–409. doi: 10.1146/annurev.iy.10.040192.002125. [DOI] [PubMed] [Google Scholar]
  37. Shimonkevitz R., Colburn C., Burnham J. A., Murray R. S., Kotzin B. L. Clonal expansions of activated gamma/delta T cells in recent-onset multiple sclerosis. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):923–927. doi: 10.1073/pnas.90.3.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sun J., Tarleton R. L. Predominance of CD8+ T lymphocytes in the inflammatory lesions of mice with acute Trypanosoma cruzi infection. Am J Trop Med Hyg. 1993 Feb;48(2):161–169. doi: 10.4269/ajtmh.1993.48.161. [DOI] [PubMed] [Google Scholar]
  39. Tarleton R. L., Koller B. H., Latour A., Postan M. Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection. Nature. 1992 Mar 26;356(6367):338–340. doi: 10.1038/356338a0. [DOI] [PubMed] [Google Scholar]
  40. Tarleton R. L., Sun J., Zhang L., Postan M. Depletion of T-cell subpopulations results in exacerbation of myocarditis and parasitism in experimental Chagas' disease. Infect Immun. 1994 May;62(5):1820–1829. doi: 10.1128/iai.62.5.1820-1829.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. d'Imperio Lima M. R., Eisen H., Minoprio P., Joskowicz M., Coutinho A. Persistence of polyclonal B cell activation with undetectable parasitemia in late stages of experimental Chagas' disease. J Immunol. 1986 Jul 1;137(1):353–356. [PubMed] [Google Scholar]
  43. dos Santos R. R., Rossi M. A., Laus J. L., Silva J. S., Savino W., Mengel J. Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi. J Exp Med. 1992 Jan 1;175(1):29–39. doi: 10.1084/jem.175.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]

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