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. 1993 Dec;61(12):5174–5180. doi: 10.1128/iai.61.12.5174-5180.1993

Gamma interferon-dependent temporary resistance to acute Toxoplasma gondii infection independent of CD4+ or CD8+ lymphocytes.

L L Johnson 1, F P VanderVegt 1, E A Havell 1
PMCID: PMC281298  PMID: 7901163

Abstract

It is well established that resistance to acute primary Toxoplasma gondii infection is mediated by a gamma interferon (IFN-gamma)-dependent mechanism. The present in vivo experiments were undertaken to investigate the cellular basis for this resistance. We show here that immunocompetent T. gondii-infected C57BL/6 (B6) mice treated with anti-IFN-gamma or with anti-Thy-1 or anti-asialo-GM1 antibodies die sooner than infected mice treated with antibodies that deplete both CD4+ and CD8+ T lymphocytes. Thy-1+ CD4- CD8- cells accumulated in the peritoneal cavities of B6 mice during the early stages of an intraperitoneal infection but did not accumulate in sham-infected control mice, and substantial numbers of Thy-1+ CD4- CD8- cells were recovered from the peritoneal cavities of infected B6 mice treated with antibodies that depleted CD4+ and CD8+ lymphocytes. Depletion of Thy-1+ cells reduced IFN-gamma to undetectable levels, whereas depletion of CD4+ and CD8+ cells did not reduce IFN-gamma levels. Thus T. gondii infection in immunocompetent B6 mice elicits Thy-1+ CD4- CD8- cells which either produce protective IFN-gamma themselves or control its production by other cells. It is likely that the function of these Thy-1+ CD4- CD8- cells is to control T. gondii tachyzoites during the early stages of primary infection before specific CD4(+)- and/or CD8(+)-dependent immunity develops.

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Selected References

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  1. Araujo F. G. Depletion of L3T4+ (CD4+) T lymphocytes prevents development of resistance to Toxoplasma gondii in mice. Infect Immun. 1991 May;59(5):1614–1619. doi: 10.1128/iai.59.5.1614-1619.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bancroft G. J., Bosma M. J., Bosma G. C., Unanue E. R. Regulation of macrophage Ia expression in mice with severe combined immunodeficiency: induction of Ia expression by a T cell-independent mechanism. J Immunol. 1986 Jul 1;137(1):4–9. [PubMed] [Google Scholar]
  3. Bancroft G. J., Schreiber R. D., Bosma G. C., Bosma M. J., Unanue E. R. A T cell-independent mechanism of macrophage activation by interferon-gamma. J Immunol. 1987 Aug 15;139(4):1104–1107. [PubMed] [Google Scholar]
  4. Dannemann B. R., Morris V. A., Araujo F. G., Remington J. S. Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts. J Immunol. 1989 Oct 15;143(8):2684–2691. [PubMed] [Google Scholar]
  5. De Paoli P., Basaglia G., Gennari D., Crovatto M., Modolo M. L., Santini G. Phenotypic profile and functional characteristics of human gamma and delta T cells during acute toxoplasmosis. J Clin Microbiol. 1992 Mar;30(3):729–731. doi: 10.1128/jcm.30.3.729-731.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunn P. L., North R. J. Early gamma interferon production by natural killer cells is important in defense against murine listeriosis. Infect Immun. 1991 Sep;59(9):2892–2900. doi: 10.1128/iai.59.9.2892-2900.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dunn P. L., North R. J. Resolution of primary murine listeriosis and acquired resistance to lethal secondary infection can be mediated predominantly by Thy-1+ CD4- CD8- cells. J Infect Dis. 1991 Nov;164(5):869–877. doi: 10.1093/infdis/164.5.869. [DOI] [PubMed] [Google Scholar]
  8. Díez B., Nicolás R., Galdeano A., Cisterna R., Cañavate M. L. Kinetics and regulation of NK activity by interleukin-2 and interferon in acute toxoplasmosis. Scand J Immunol. 1991 Nov;34(5):673–677. doi: 10.1111/j.1365-3083.1991.tb01591.x. [DOI] [PubMed] [Google Scholar]
  9. Gazzinelli R. T., Hakim F. T., Hieny S., Shearer G. M., Sher A. Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J Immunol. 1991 Jan 1;146(1):286–292. [PubMed] [Google Scholar]
  10. Gazzinelli R. T., Hieny S., Wynn T. A., Wolf S., Sher A. Interleukin 12 is required for the T-lymphocyte-independent induction of interferon gamma by an intracellular parasite and induces resistance in T-cell-deficient hosts. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6115–6119. doi: 10.1073/pnas.90.13.6115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gazzinelli R., Xu Y., Hieny S., Cheever A., Sher A. Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii. J Immunol. 1992 Jul 1;149(1):175–180. [PubMed] [Google Scholar]
  12. Hauser W. E., Jr, Sharma S. D., Remington J. S. Natural killer cells induced by acute and chronic toxoplasma infection. Cell Immunol. 1982 May 15;69(2):330–346. doi: 10.1016/0008-8749(82)90076-4. [DOI] [PubMed] [Google Scholar]
  13. Hauser W. E., Jr, Tsai V. Acute toxoplasma infection of mice induces spleen NK cells that are cytotoxic for T. gondii in vitro. J Immunol. 1986 Jan;136(1):313–319. [PubMed] [Google Scholar]
  14. Havell E. A. Purification and further characterization of an anti-murine interferon-gamma monoclonal neutralizing antibody. J Interferon Res. 1986 Oct;6(5):489–497. doi: 10.1089/jir.1986.6.489. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hughes H. P., Kasper L. H., Little J., Dubey J. P. Absence of a role for natural killer cells in the control of acute infection by Toxoplasma gondii oocysts. Clin Exp Immunol. 1988 Jun;72(3):394–399. [PMC free article] [PubMed] [Google Scholar]
  17. Inoue T., Yoshikai Y., Matsuzaki G., Nomoto K. Early appearing gamma/delta-bearing T cells during infection with Calmétte Guérin bacillus. J Immunol. 1991 Apr 15;146(8):2754–2762. [PubMed] [Google Scholar]
  18. Izzo A. A., North R. J. Evidence for an alpha/beta T cell-independent mechanism of resistance to mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+ and CD8+ T cells. J Exp Med. 1992 Aug 1;176(2):581–586. doi: 10.1084/jem.176.2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnson L. L. A protective role for endogenous tumor necrosis factor in Toxoplasma gondii infection. Infect Immun. 1992 May;60(5):1979–1983. doi: 10.1128/iai.60.5.1979-1983.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Johnson L. L. SCID mouse models of acute and relapsing chronic Toxoplasma gondii infections. Infect Immun. 1992 Sep;60(9):3719–3724. doi: 10.1128/iai.60.9.3719-3724.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kamiyama T., Hagiwara T. Augmented followed by suppressed levels of natural cell-mediated cytotoxicity in mice infected with Toxoplasma gondii. Infect Immun. 1982 May;36(2):628–636. doi: 10.1128/iai.36.2.628-636.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Khan I. A., Ely K. H., Kasper L. H. A purified parasite antigen (p30) mediates CD8+ T cell immunity against fatal Toxoplasma gondii infection in mice. J Immunol. 1991 Nov 15;147(10):3501–3506. [PubMed] [Google Scholar]
  23. Matsuzaki G., Hiromatsu K., Yoshikai Y., Muramori K., Nomoto K. Characterization of T-cell receptor gamma delta T cells appearing at the early phase of murine Listeria monocytogenes infection. Immunology. 1993 Jan;78(1):22–27. [PMC free article] [PubMed] [Google Scholar]
  24. Nagasawa H., Manabe T., Maekawa Y., Oka M., Himeno K. Role of L3T4+ and Lyt-2+ T cell subsets in protective immune responses of mice against infection with a low or high virulent strain of Toxoplasma gondii. Microbiol Immunol. 1991;35(3):215–222. doi: 10.1111/j.1348-0421.1991.tb01550.x. [DOI] [PubMed] [Google Scholar]
  25. Ohga S., Yoshikai Y., Takeda Y., Hiromatsu K., Nomoto K. Sequential appearance of gamma/delta- and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes. Eur J Immunol. 1990 Mar;20(3):533–538. doi: 10.1002/eji.1830200311. [DOI] [PubMed] [Google Scholar]
  26. Parker S. J., Roberts C. W., Alexander J. CD8+ T cells are the major lymphocyte subpopulation involved in the protective immune response to Toxoplasma gondii in mice. Clin Exp Immunol. 1991 May;84(2):207–212. doi: 10.1111/j.1365-2249.1991.tb08150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Scalise F., Gerli R., Castellucci G., Spinozzi F., Fabietti G. M., Crupi S., Sensi L., Britta R., Vaccaro R., Bertotto A. Lymphocytes bearing the gamma delta T-cell receptor in acute toxoplasmosis. Immunology. 1992 Aug;76(4):668–670. [PMC free article] [PubMed] [Google Scholar]
  29. Schlüter D., Deckert-Schlüter M., Schwendemann G., Brunner H., Hof H. Expression of major histocompatibility complex class II antigens and levels of interferon-gamma, tumour necrosis factor, and interleukin-6 in cerebrospinal fluid and serum in Toxoplasma gondii-infected SCID and immunocompetent C.B-17 mice. Immunology. 1993 Mar;78(3):430–435. [PMC free article] [PubMed] [Google Scholar]
  30. Sher A., Oswald I. P., Hieny S., Gazzinelli R. T. Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha. J Immunol. 1993 May 1;150(9):3982–3989. [PubMed] [Google Scholar]
  31. Suzuki Y., Orellana M. A., Schreiber R. D., Remington J. S. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988 Apr 22;240(4851):516–518. doi: 10.1126/science.3128869. [DOI] [PubMed] [Google Scholar]
  32. Suzuki Y., Remington J. S. Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice. J Immunol. 1988 Jun 1;140(11):3943–3946. [PubMed] [Google Scholar]
  33. Wherry J. C., Schreiber R. D., Unanue E. R. Regulation of gamma interferon production by natural killer cells in scid mice: roles of tumor necrosis factor and bacterial stimuli. Infect Immun. 1991 May;59(5):1709–1715. doi: 10.1128/iai.59.5.1709-1715.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]

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