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. 1993 Dec;61(12):5129–5133. doi: 10.1128/iai.61.12.5129-5133.1993

Differential susceptibilities of mice genomically deleted of CD4 and CD8 to infections with Trypanosoma cruzi or Trypanosoma brucei.

M E Rottenberg 1, M Bakhiet 1, T Olsson 1, K Kristensson 1, T Mak 1, H Wigzell 1, A Orn 1
PMCID: PMC281292  PMID: 8225589

Abstract

The role of CD4+ and CD8+ T cells in the surveillance of Trypanosoma cruzi or Trypanosoma brucei brucei was studied in mice which lacked CD4 or CD8 molecules and which were generated by embryonic stem cell technology. Whereas wild-type mice infected with T. cruzi (Tulahuén strain) displayed low levels of parasitemia and no mortality, striking increases in parasite growth and mortality occurred in both CD8- and CD4- mice. On the contrary, CD8- and, to a lesser degree, CD4- mice showed enhanced resistance to T. b. brucei. T-cell-dependent immunoglobulin G-specific responses were produced in CD8- but not CD4- mice. Normal T-cell proliferative responses were measured in both CD4- and CD8- mice. Interleukin-4 production after concanavalin A or anti-CD3 monoclonal antibody stimulation was strikingly enhanced in CD8- but not CD4- spleen cells, whereas gamma interferon production was normal in both CD4- and CD8- spleen cells. Spleen and lymph node cells from CD8- (but not CD4-) mice at 20 days postinfection with T. cruzi had higher levels of interleukin-4 mRNA than the wild-type controls, as shown in a competitive polymerase chain reaction assay. On the other hand, CD4- (but not CD8-) mice at 20 days postinfection with T. cruzi had lower levels of gamma interferon mRNA than the wild-type mice.

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Selected References

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  1. Araujo F. G. Development of resistance to Trypanosoma cruzi in mice depends on a viable population of L3T4+ (CD4+) T lymphocytes. Infect Immun. 1989 Jul;57(7):2246–2248. doi: 10.1128/iai.57.7.2246-2248.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bakhiet M., Olsson T., Edlund C., Höjeberg B., Holmberg K., Lorentzen J., Kristensson K. A Trypanosoma brucei brucei-derived factor that triggers CD8+ lymphocytes to interferon-gamma secretion: purification, characterization and protective effects in vivo by treatment with a monoclonal antibody against the factor. Scand J Immunol. 1993 Feb;37(2):165–178. doi: 10.1111/j.1365-3083.1993.tb01753.x. [DOI] [PubMed] [Google Scholar]
  3. Bakhiet M., Olsson T., van der Meide P., Kristensson K. Depletion of CD8+ T cells suppresses growth of Trypanosoma brucei brucei and interferon-gamma) production in infected rats. Clin Exp Immunol. 1990 Aug;81(2):195–199. doi: 10.1111/j.1365-2249.1990.tb03317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brener Z. Immunity to Trypanosoma cruzi. Adv Parasitol. 1980;18:247–292. doi: 10.1016/s0065-308x(08)60401-7. [DOI] [PubMed] [Google Scholar]
  5. Fung-Leung W. P., Schilham M. W., Rahemtulla A., Kündig T. M., Vollenweider M., Potter J., van Ewijk W., Mak T. W. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell. 1991 May 3;65(3):443–449. doi: 10.1016/0092-8674(91)90462-8. [DOI] [PubMed] [Google Scholar]
  6. Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  8. Kierszenbaum F., Pienkowski M. M. Thymus-dependent control of host defense mechanisms against Trypanosoma cruzi infection. Infect Immun. 1979 Apr;24(1):117–120. doi: 10.1128/iai.24.1.117-120.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. McCabe R. E., Meagher S. G., Mullins B. T. Endogenous interferon-gamma, macrophage activation, and murine host defense against acute infection with Trypanosoma cruzi. J Infect Dis. 1991 Apr;163(4):912–915. doi: 10.1093/infdis/163.4.912. [DOI] [PubMed] [Google Scholar]
  10. McCabe R. E., Remington J. S., Araujo F. G. In vivo and in vitro effects of cyclosporin A on Trypanosoma cruzi. Am J Trop Med Hyg. 1985 Sep;34(5):861–865. doi: 10.4269/ajtmh.1985.34.861. [DOI] [PubMed] [Google Scholar]
  11. Olsson T., Bakhiet M., Edlund C., Höjeberg B., Van der Meide P. H., Kristensson K. Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth. Eur J Immunol. 1991 Oct;21(10):2447–2454. doi: 10.1002/eji.1830211022. [DOI] [PubMed] [Google Scholar]
  12. Olsson T., Bakhiet M., Höjeberg B., Ljungdahl A., Edlund C., Andersson G., Ekre H. P., Fung-Leung W. P., Mak T., Wigzell H. CD8 is critically involved in lymphocyte activation by a T. brucei brucei-released molecule. Cell. 1993 Mar 12;72(5):715–727. doi: 10.1016/0092-8674(93)90400-k. [DOI] [PubMed] [Google Scholar]
  13. Petray P. B., Rottenberg M. E., Bertot G., Corral R. S., Diaz A., Orn A., Grinstein S. Effect of anti-gamma-interferon and anti-interleukin-4 administration on the resistance of mice against infection with reticulotropic and myotropic strains of Trypanosoma cruzi. Immunol Lett. 1993 Jan;35(1):77–80. doi: 10.1016/0165-2478(93)90151-q. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Rahemtulla A., Fung-Leung W. P., Schilham M. W., Kündig T. M., Sambhara S. R., Narendran A., Arabian A., Wakeham A., Paige C. J., Zinkernagel R. M. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 1991 Sep 12;353(6340):180–184. doi: 10.1038/353180a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Reinitz D. M., Mansfield J. M. T-cell-independent and T-cell-dependent B-cell responses to exposed variant surface glycoprotein epitopes in trypanosome-infected mice. Infect Immun. 1990 Jul;58(7):2337–2342. doi: 10.1128/iai.58.7.2337-2342.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rottenberg M., Cardoni R. L., Andersson R., Segura E. L., Orn A. Role of T helper/inducer cells as well as natural killer cells in resistance to Trypanosoma cruzi infection. Scand J Immunol. 1988 Nov;28(5):573–582. doi: 10.1111/j.1365-3083.1988.tb01489.x. [DOI] [PubMed] [Google Scholar]
  19. Russo M., Starobinas N., Minoprio P., Coutinho A., Hontebeyrie-Joskowicz M. Parasitic load increases and myocardial inflammation decreases in Trypanosoma cruzi-infected mice after inactivation of helper T cells. Ann Inst Pasteur Immunol. 1988 May-Jun;139(3):225–236. doi: 10.1016/0769-2625(88)90136-5. [DOI] [PubMed] [Google Scholar]
  20. Schmunis G. A., Cappa S. M., Traversa O. C., Janovsky J. F. The effect of immuno-depression due to neonatal thymectomy on infections with Trypanosoma cruzi in mice. Trans R Soc Trop Med Hyg. 1971;65(1):89–94. doi: 10.1016/0035-9203(71)90190-8. [DOI] [PubMed] [Google Scholar]
  21. Sher A., Gazzinelli R. T., Oswald I. P., Clerici M., Kullberg M., Pearce E. J., Berzofsky J. A., Mosmann T. R., James S. L., Morse H. C., 3rd Role of T-cell derived cytokines in the downregulation of immune responses in parasitic and retroviral infection. Immunol Rev. 1992 Jun;127:183–204. doi: 10.1111/j.1600-065x.1992.tb01414.x. [DOI] [PubMed] [Google Scholar]
  22. Silva J. S., Morrissey P. J., Grabstein K. H., Mohler K. M., Anderson D., Reed S. G. Interleukin 10 and interferon gamma regulation of experimental Trypanosoma cruzi infection. J Exp Med. 1992 Jan 1;175(1):169–174. doi: 10.1084/jem.175.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tarleton R. L. Depletion of CD8+ T cells increases susceptibility and reverses vaccine-induced immunity in mice infected with Trypanosoma cruzi. J Immunol. 1990 Jan 15;144(2):717–724. [PubMed] [Google Scholar]
  24. 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]
  25. Wirth J. J., Kierszenbaum F., Sonnenfeld G., Zlotnik A. Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi. Infect Immun. 1985 Jul;49(1):61–66. doi: 10.1128/iai.49.1.61-66.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

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