Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Apr 1;171(4):1141–1154. doi: 10.1084/jem.171.4.1141

Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon gamma in listerial infection

PMCID: PMC2187836  PMID: 2109036

Abstract

Studies were made on the effects of in vivo administration of anti-CD4 mAb, anti-CD8 mAb, or a combination of both mAbs on multiplication of bacteria, the levels of serum transaminases, and mortality in mice infected with Listeria monocytogenes. Results showed that in sublethal infection, CD8+ cells enhanced the peak of bacterial multiplication and liver cell necrosis, and CD4+ cells suppressed CD8+ cell-mediated enhancement. Results also showed that either CD4+ or CD8+ cells were necessary for, and capable of, mediating clearance of the bacteria. CD8+ cells were more efficient than CD4+ cells, but for optimal clearance both were necessary. In lethal listeriosis, treatment of mice with anti-CD8 mAb or a combination of both anti-CD4 and anti-CD8 mAbs, but not anti-CD4 mAb only, protected mice from death by decreasing multiplication of bacteria in the liver and spleen after a peak of approximately 10(8) CFU, and lowering the elevated serum levels of transaminases. These findings indicated that CD8+ cells were responsible for causing irreversible systemic Listeria infection and severe liver necrosis. In lethal listeriosis, administration of rMuIFN- gamma markedly prolonged survival by decreasing multiplication of bacteria and promoting recovery from liver necrosis.

Full Text

The Full Text of this article is available as a PDF (824.7 KB).

Selected References

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

  1. Bishop D. K., Hinrichs D. J. Adoptive transfer of immunity to Listeria monocytogenes. The influence of in vitro stimulation on lymphocyte subset requirements. J Immunol. 1987 Sep 15;139(6):2005–2009. [PubMed] [Google Scholar]
  2. Buchmeier N. A., Schreiber R. D. Requirement of endogenous interferon-gamma production for resolution of Listeria monocytogenes infection. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7404–7408. doi: 10.1073/pnas.82.21.7404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen-Woan M., Sajewski D. H., McGregor D. D. T-cell co-operation in the mediation of acquired resistance to Listeria monocytogenes. Immunology. 1985 Sep;56(1):33–42. [PMC free article] [PubMed] [Google Scholar]
  4. Czuprynski C. J., Brown J. F. Dual regulation of anti-bacterial resistance and inflammatory neutrophil and macrophage accumulation by L3T4+ and Lyt 2+ Listeria-immune T cells. Immunology. 1987 Feb;60(2):287–293. [PMC free article] [PubMed] [Google Scholar]
  5. Czuprynski C. J., Brown J. F., Young K. M., Cooley A. J. Administration of purified anti-L3T4 monoclonal antibody impairs the resistance of mice to Listeria monocytogenes infection. Infect Immun. 1989 Jan;57(1):100–109. doi: 10.1128/iai.57.1.100-109.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Libero G., Kaufmann S. H. Antigen-specific Lyt-2+ cytolytic T lymphocytes from mice infected with the intracellular bacterium Listeria monocytogenes. J Immunol. 1986 Oct 15;137(8):2688–2694. [PubMed] [Google Scholar]
  7. De Maeyer-Guignard J., De Maeyer E. Immunomodulation by interferons: recent developments. Interferon. 1985;6:69–91. [PubMed] [Google Scholar]
  8. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  9. Hahn H., Kaufmann S. H. The role of cell-mediated immunity in bacterial infections. Rev Infect Dis. 1981 Nov-Dec;3(6):1221–1250. doi: 10.1093/clinids/3.6.1221. [DOI] [PubMed] [Google Scholar]
  10. Ichikawa T., Nakayama E., Uenaka A., Monden M., Mori T. Effector cells in allelic H-2 class I-incompatible skin graft rejection. J Exp Med. 1987 Oct 1;166(4):982–990. doi: 10.1084/jem.166.4.982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kaufmann S. H., Hahn H., Berger R., Kirchner H. Interferon-gamma production by Listeria monocytogenes-specific T cells active in cellular antibacterial immunity. Eur J Immunol. 1983 Mar;13(3):265–268. doi: 10.1002/eji.1830130318. [DOI] [PubMed] [Google Scholar]
  12. Kaufmann S. H., Hug E., Väth U., Müller I. Effective protection against Listeria monocytogenes and delayed-type hypersensitivity to listerial antigens depend on cooperation between specific L3T4+ and Lyt 2+ T cells. Infect Immun. 1985 Apr;48(1):263–266. doi: 10.1128/iai.48.1.263-266.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kiderlen A. F., Kaufmann S. H., Lohmann-Matthes M. L. Protection of mice against the intracellular bacterium Listeria monocytogenes by recombinant immune interferon. Eur J Immunol. 1984 Oct;14(10):964–967. doi: 10.1002/eji.1830141019. [DOI] [PubMed] [Google Scholar]
  14. Landolfo S., Cofano F., Giovarelli M., Prat M., Cavallo G., Forni G. Inhibition of interferon-gamma may suppress allograft reactivity by T lymphocytes in vitro and in vivo. Science. 1985 Jul 12;229(4709):176–179. doi: 10.1126/science.3160110. [DOI] [PubMed] [Google Scholar]
  15. Lane F. C., Unanue E. R. Requirement of thymus (T) lymphocytes for resistance to listeriosis. J Exp Med. 1972 May 1;135(5):1104–1112. doi: 10.1084/jem.135.5.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Mielke M. E., Ehlers S., Hahn H. T-cell subsets in delayed-type hypersensitivity, protection, and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity. Infect Immun. 1988 Aug;56(8):1920–1925. doi: 10.1128/iai.56.8.1920-1925.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mielke M. E., Niedobitek G., Stein H., Hahn H. Acquired resistance to Listeria monocytogenes is mediated by Lyt-2+ T cells independently of the influx of monocytes into granulomatous lesions. J Exp Med. 1989 Aug 1;170(2):589–594. doi: 10.1084/jem.170.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Murray H. W., Rubin B. Y., Rothermel C. D. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest. 1983 Oct;72(4):1506–1510. doi: 10.1172/JCI111107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakane A., Minagawa T., Yasuda I., Yu C., Kato K. Prevention by gamma interferon of fatal infection with Listeria monocytogenes in mice treated with cyclosporin A. Infect Immun. 1988 Aug;56(8):2011–2015. doi: 10.1128/iai.56.8.2011-2015.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakayama E., Uenaka A. Effect of in vivo administration of Lyt antibodies. Lyt phenotype of T cells in lymphoid tissues and blocking of tumor rejection. J Exp Med. 1985 Feb 1;161(2):345–355. doi: 10.1084/jem.161.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nathan C. F., Prendergast T. J., Wiebe M. E., Stanley E. R., Platzer E., Remold H. G., Welte K., Rubin B. Y., Murray H. W. Activation of human macrophages. Comparison of other cytokines with interferon-gamma. J Exp Med. 1984 Aug 1;160(2):600–605. doi: 10.1084/jem.160.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Newborg M. F., North R. J. On the mechanism of T cell-independent anti-Listeria resistance in nude mice. J Immunol. 1980 Feb;124(2):571–576. [PubMed] [Google Scholar]
  24. North R. J. Cellular mediators of anti-Listeria immunity as an enlarged population of short lived, replicating T cells. Kinetics of their production. J Exp Med. 1973 Aug 1;138(2):342–355. doi: 10.1084/jem.138.2.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. North R. J. The relative importance of blood monocytes and fixed macrophages to the expression of cell-mediated immunity to infection. J Exp Med. 1970 Sep 1;132(3):521–534. doi: 10.1084/jem.132.3.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Näher H., Sperling U., Takacs L., Hahn H. Dynamics of T cells of L3T4 and Ly 2 phenotype within granulomas in murine listeriosis. Clin Exp Immunol. 1985 Jun;60(3):559–564. [PMC free article] [PubMed] [Google Scholar]
  27. Pace J. L., Russell S. W., Torres B. A., Johnson H. M., Gray P. W. Recombinant mouse gamma interferon induces the priming step in macrophage activation for tumor cell killing. J Immunol. 1983 May;130(5):2011–2013. [PubMed] [Google Scholar]
  28. Rosen H., Gordon S., North R. J. Exacerbation of murine listeriosis by a monoclonal antibody specific for the type 3 complement receptor of myelomonocytic cells. Absence of monocytes at infective foci allows Listeria to multiply in nonphagocytic cells. J Exp Med. 1989 Jul 1;170(1):27–37. doi: 10.1084/jem.170.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schofield L., Ferreira A., Altszuler R., Nussenzweig V., Nussenzweig R. S. Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro. J Immunol. 1987 Sep 15;139(6):2020–2025. [PubMed] [Google Scholar]
  30. Simon P. L., Farrar J. J., Dind P. D. Biochemical relationship between murine immune interferon and a killer cell helper factor. J Immunol. 1979 Jan;122(1):127–132. [PubMed] [Google Scholar]
  31. Zinkernagel R. M. Speculations on the role of major transplantation antigens in cell-mediated immunity against intracellular parasites. Curr Top Microbiol Immunol. 1978;82:113–138. doi: 10.1007/978-3-642-46388-4_4. [DOI] [PubMed] [Google Scholar]
  32. van Dissel J. T., Stikkelbroeck J. J., van den Barselaar M. T., Sluiter W., Leijh P. C., van Furth R. Divergent changes in antimicrobial activity after immunologic activation of mouse peritoneal macrophages. J Immunol. 1987 Sep 1;139(5):1665–1672. [PubMed] [Google Scholar]

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

RESOURCES