Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Mar 1;139(3):560–580. doi: 10.1084/jem.139.3.560

CELL-MEDIATED IMMUNITY AGAINST BESNOITIA AND TOXOPLASMA IN SPECIFICALLY AND CROSS-IMMUNIZED HAMSTERS AND IN CULTURES

Richard L Hoff 1, J K Frenkel 1
PMCID: PMC2139559  PMID: 4812629

Abstract

The capacity of hamster peritoneal cell populations to control viability and growth of Besnoitia and Toxoplasma organisms was assessed in vivo and in vitro. Immunized hamsters reduced the homologous organisms 100- to 10,000-fold over a 5-day period, but the heterologous infection increased 100- to 1,000-fold in numbers, similar as in the nonimmune controls. Passively administered antibody was ineffective although lytic cofactors were supplied by hamsters. In cultures, peritoneal cells from Besnoitia-immune hamsters delayed the growth of homologous parasites to an average of 38.5 h per division; however, in Toxoplasma-immune and nonimmune cells, Besnoitia divided every 12.8 h. Specificity of immunity was pronounced against both infections. With cross-infections, Toxoplasma-immune cultures did not effectively delay Besnoitia growth; however, Besnoitia-immune cultures reduced Toxoplasma growth by one-half. Co-cultivation experiments demonstrated that specifically committed lymphocytes could instruct macrophages to reduce the homologous organism 10-fold, whereas heterologous organisms were reduced only 2-fold. Lymphocyte supernatants initiated hypersensitivity as indicated by macrophage activation and giant cell formation in culture. However, these supernatants did not transfer infection immunity. Lymphokines could account for the hypersensitivity phenomena, but cell-mediated infection immunity in this model required close lymphocyte-macrophage proximity. These studies indicate that a number of distinct processes including delayed hypersensitivity, macrophage activation, and specific cellular immunity are acting simultaneously during latent Besnoitia infection of hamsters. All three processes are mediated by lymphoid cells and appear to be specifically induced. Although activated macrophages develop some heightened nonspecific capabilities, these were several orders of magnitude below the specific effects.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amos H. E., Lachmann P. J. The immunological specificity of a macrophage inhibition factor. Immunology. 1970 Feb;18(2):269–278. [PMC free article] [PubMed] [Google Scholar]
  2. Biesecker J. L. Cellular and humoral immunity after allogeneic transplantation in the rat. I. Cellular and humoral immunity of measured by a 51 Cr cytotoxicity assay after allogeneic tumor and renal transplantation. Transplantation. 1973 Mar;15(3):298–307. doi: 10.1097/00007890-197303000-00006. [DOI] [PubMed] [Google Scholar]
  3. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. II. Passive transfer of recovery mechanisms with immune lymphoid cells. J Exp Med. 1971 May 1;133(5):1074–1089. doi: 10.1084/jem.133.5.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bloom B. R., Maillard J., Gaffney J., Kano S., Shevach E., Green I. The virus plaque assay and the effector cell in cell-mediated immune reactions. Transplant Proc. 1972 Sep;4(3):329–334. [PubMed] [Google Scholar]
  5. Bommer W. The life cycle of virulent toxoplasma in cell cultures. Aust J Exp Biol Med Sci. 1969 Aug;47(4):505–512. doi: 10.1038/icb.1969.54. [DOI] [PubMed] [Google Scholar]
  6. Clarke J. A., Salsbury A. J., Willoughby D. A. Some scanning electron-microscope observations on stimulated lymphocytes. J Pathol. 1971 Jun;104(2):115–118. doi: 10.1002/path.1711040205. [DOI] [PubMed] [Google Scholar]
  7. David J. R. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci U S A. 1966 Jul;56(1):72–77. doi: 10.1073/pnas.56.1.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dvorak A. M., Hammond M. E., Dvorak H. F., Karnovsky M. J. Loss of cell surface material from peritoneal exudate cells associated with lymphocyte-mediated inhibition of macrophage migration from capillary tubes. Lab Invest. 1972 Dec;27(6):561–574. [PubMed] [Google Scholar]
  9. EVANS V. J., BRYANT J. C., FIORAMONTI M. C., MCQUILKIN W. T., SANFORD K. K., EARLE W. R. Studies of nutrient media for tissue cells in vitro. I. A protein-free chemically defined medium for cultivation of strain L cells. Cancer Res. 1956 Jan;16(1):77–86. [PubMed] [Google Scholar]
  10. Evans R., Grant C. K., Cox H., Steele K., Alexander P. Thymus-derived lymphocytes produce an immunologically specific macrophage-arming factor. J Exp Med. 1972 Nov 1;136(5):1318–1322. doi: 10.1084/jem.136.5.1318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FRENKEL J. K. Effects of hormones on the adrenal necrosis produced by Besnoitia jellisoni in golden hamsters. J Exp Med. 1956 Mar 1;103(3):375–398. doi: 10.1084/jem.103.3.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fowles R. E., Fajardo I. M., Leibowitch J. L., David J. R. The enhancement of macrophage bacteriostasis by products of activated lymphocytes. J Exp Med. 1973 Oct 1;138(4):952–964. doi: 10.1084/jem.138.4.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Frenkel J. K. Adoptive immunity to intracellular infection. J Immunol. 1967 Jun;98(6):1309–1319. [PubMed] [Google Scholar]
  14. Frenkel J. K. Infection and immunity in hamsters. Prog Exp Tumor Res. 1972;16:326–367. [PubMed] [Google Scholar]
  15. Frenkel J. K., Lunde M. N. Effects of corticosteroids on antibody and immunity in Besnoitia infection of hamsters. J Infect Dis. 1966 Oct;116(4):414–424. doi: 10.1093/infdis/116.4.414. [DOI] [PubMed] [Google Scholar]
  16. Frenkel J. K., Wilson H. R. Effects of radiation on specific cellular immunities: besnoitiosis and a herpesvirus infection of hamsters. J Infect Dis. 1972 Mar;125(3):216–230. doi: 10.1093/infdis/125.3.216. [DOI] [PubMed] [Google Scholar]
  17. Freshman M. M., Merigan T. C., Remington J. S., Brownlee I. E. In vitro and in vivo antiviral action of an interferon-like substance induced by Toxoplasma gondii. Proc Soc Exp Biol Med. 1966 Dec;123(3):862–866. doi: 10.3181/00379727-123-31625. [DOI] [PubMed] [Google Scholar]
  18. Garrie S. A., Wolf-Jurgensen P. Comparison of methods of counting skin window coverslips. A statistical analysis. J Allergy Clin Immunol. 1972 Apr;49(4):238–244. doi: 10.1016/0091-6749(72)90086-3. [DOI] [PubMed] [Google Scholar]
  19. Jones G. Release of surface receptors from lymphocytes. J Immunol. 1973 Jun;110(6):1526–1531. [PubMed] [Google Scholar]
  20. Jones T. C., Hirsch J. G. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med. 1972 Nov 1;136(5):1173–1194. doi: 10.1084/jem.136.5.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. KAUFMAN H. E., MALONEY E. D. Multiplication of three strains of Toxoplasma gondii in tissue culture. J Parasitol. 1962 Jun;48:358–361. [PubMed] [Google Scholar]
  22. Klun C. L., Youmans G. P. The induction by Listeria monocytogenes and plant mitogens of lymphocyte supernatant fluids which inhibit the growth of Mycobacterium tuberculosis within macrophages in vitro. J Reticuloendothel Soc. 1973 Mar;13(3):275–285. [PubMed] [Google Scholar]
  23. Koster F. T., McGregor D. D. The mediator of cellular immunity. 3. Lymphocyte traffic from the blood into the inflamed peritoneal cavity. J Exp Med. 1971 Apr 1;133(4):864–876. doi: 10.1084/jem.133.4.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Krahenbuhl J. L., Remington J. S. In vitro induction of nonspecific resistance in macrophages by specifically sensitized lymphocytes. Infect Immun. 1971 Oct;4(4):337–343. doi: 10.1128/iai.4.4.337-343.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. LUNDE M. N., JACOBS L. ANTIGENIC RELATIONSHIP OF TOXOPLASMA GONDII AND BESNOITIA JELLISONI. J Parasitol. 1965 Apr;51:273–276. [PubMed] [Google Scholar]
  26. MACKANESS G. B. Cellular resistance to infection. J Exp Med. 1962 Sep 1;116:381–406. doi: 10.1084/jem.116.3.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mackaness G. B. The influence of immunologically committed lymphoid cells on macrophage activity in vivo. J Exp Med. 1969 May 1;129(5):973–992. doi: 10.1084/jem.129.5.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Marker O., Volkert M. Studies on cell-mediated immunity to lymphocytic choriomeningitis virus in mice. J Exp Med. 1973 Jun 1;137(6):1511–1525. doi: 10.1084/jem.137.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Matsubayashi H., Akao S. Immuno-electron microscopic studies on toxoplasma gondii. Am J Trop Med Hyg. 1966 Jul;15(4):486–491. doi: 10.4269/ajtmh.1966.15.486. [DOI] [PubMed] [Google Scholar]
  30. Mosier D. E. Cell interactions in the primary immune response in vitro: a requirement for specific cell clusters. J Exp Med. 1969 Feb 1;129(2):351–362. doi: 10.1084/jem.129.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Neiburger R. G., Youmans G. P., Youmans A. S. Relationship between tuberculin hypersensitivity and cellular immunity to infection in mice vaccinated with viable attenuated Mycobacterial cells or with Mycobacterial ribonucleic acid preparations. Infect Immun. 1973 Jul;8(1):42–47. doi: 10.1128/iai.8.1.42-47.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rytel M. W., Jones T. C. Induction of interferon in mice infected with Toxoplasma gondii. Proc Soc Exp Biol Med. 1966 Dec;123(3):859–862. doi: 10.3181/00379727-123-31624. [DOI] [PubMed] [Google Scholar]
  33. Sabin A. B., Feldman H. A. Dyes as Microchemical Indicators of a New Immunity Phenomenon Affecting a Protozoon Parasite (Toxoplasma). Science. 1948 Dec 10;108(2815):660–663. doi: 10.1126/science.108.2815.660. [DOI] [PubMed] [Google Scholar]
  34. Simon H. B., Sheagren J. N. Migration inhibitory factor and macrophage bactericidal function. Infect Immun. 1972 Aug;6(2):101–103. doi: 10.1128/iai.6.2.101-103.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Takemoto K. K., Habel K. Hamster ascitic fluids containing complement-fixing antibody against virus-induced tumor antigens. Proc Soc Exp Biol Med. 1965 Oct;120(1):124–127. doi: 10.3181/00379727-120-30464. [DOI] [PubMed] [Google Scholar]
  36. Unanue E. R., Cerottini J. C. The function of macrophages in the immune response. Semin Hematol. 1970 Apr;7(2):225–248. [PubMed] [Google Scholar]
  37. Watanabe K., Mitsuhashi S. The role of transfer agent in immunity. Tohoku J Exp Med. 1971 Jan;103(1):1–6. doi: 10.1620/tjem.103.1. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES