Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1993 Oct;67(10):6299–6302. doi: 10.1128/jvi.67.10.6299-6302.1993

Divergence between cytotoxic effector function and tumor necrosis factor alpha production for inflammatory CD4+ T cells from mice with Sendai virus pneumonia.

S Hou 1, M Fishman 1, K G Murti 1, P C Doherty 1
PMCID: PMC238057  PMID: 8396684

Abstract

Sendai virus pneumonia in beta 2-microglobulin-deficient [beta 2-m(-/-)] mice lacking CD8+ T cells is characterized by the development of CD4+ cytotoxic T lymphocytes that can be recovered directly from the respiratory tract. These CD4+ cytotoxic T lymphocytes are not found in beta 2-m (+/+) mice, though inflammatory CD4+ T cells from both beta 2-m (-/-) and beta 2-m (+/+) mice produce substantial amounts of tumor necrosis factor alpha. Blocking experiments with a monoclonal antibody that also inhibits tumor necrosis factor beta show that the secreted forms of these two cytokines are not responsible for virus-specific killing of class II major histocompatibility complex-compatible targets. Comparison of electron micrographs indicates that the CD4+ effectors from the beta 2-m (-/-) mice are potent inducers of apoptosis, while this is not the case for the beta 2-m (+/+) CD4+ set. These experiments further define the functional status of virus-specific CD4+ T cells responding in vivo in the presence or absence of CD8+ effectors.

Full text

PDF
6300

Images in this article

6301Image
on p.6301

Selected References

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

  1. Allan W., Tabi Z., Cleary A., Doherty P. C. Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J Immunol. 1990 May 15;144(10):3980–3986. [PubMed] [Google Scholar]
  2. Apasov S., Redegeld F., Sitkovsky M. Cell-mediated cytotoxicity: contact and secreted factors. Curr Opin Immunol. 1993 Jun;5(3):404–410. doi: 10.1016/0952-7915(93)90060-6. [DOI] [PubMed] [Google Scholar]
  3. Bender B. S., Croghan T., Zhang L., Small P. A., Jr Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med. 1992 Apr 1;175(4):1143–1145. doi: 10.1084/jem.175.4.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berent S. L., Torczynski R. M., Bollon A. P. Sendai virus induces high levels of tumor necrosis factor mRNA in human peripheral blood leukocytes. Nucleic Acids Res. 1986 Nov 25;14(22):8997–9015. doi: 10.1093/nar/14.22.8997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Browning J. L., Ngam-ek A., Lawton P., DeMarinis J., Tizard R., Chow E. P., Hession C., O'Brine-Greco B., Foley S. F., Ware C. F. Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell. 1993 Mar 26;72(6):847–856. doi: 10.1016/0092-8674(93)90574-a. [DOI] [PubMed] [Google Scholar]
  6. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992;10:267–293. doi: 10.1146/annurev.iy.10.040192.001411. [DOI] [PubMed] [Google Scholar]
  7. Eichelberger M., Allan W., Zijlstra M., Jaenisch R., Doherty P. C. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med. 1991 Oct 1;174(4):875–880. doi: 10.1084/jem.174.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fiette L., Aubert C., Brahic M., Rossi C. P. Theiler's virus infection of beta 2-microglobulin-deficient mice. J Virol. 1993 Jan;67(1):589–592. doi: 10.1128/jvi.67.1.589-592.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fishman M. Cytolytic activities of activated macrophages versus paraformaldehyde-fixed macrophages; soluble versus membrane-associated TNF. Cell Immunol. 1991 Oct 1;137(1):164–174. doi: 10.1016/0008-8749(91)90066-k. [DOI] [PubMed] [Google Scholar]
  10. Hou S., Doherty P. C., Zijlstra M., Jaenisch R., Katz J. M. Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. J Immunol. 1992 Aug 15;149(4):1319–1325. [PubMed] [Google Scholar]
  11. Koller B. H., Smithies O. Altering genes in animals by gene targeting. Annu Rev Immunol. 1992;10:705–730. doi: 10.1146/annurev.iy.10.040192.003421. [DOI] [PubMed] [Google Scholar]
  12. Lehmann-Grube F., Löhler J., Utermöhlen O., Gegin C. Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene. J Virol. 1993 Jan;67(1):332–339. doi: 10.1128/jvi.67.1.332-339.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Liu A. Y., Miskovsky E. P., Stanhope P. E., Siliciano R. F. Production of transmembrane and secreted forms of tumor necrosis factor (TNF)-alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones. Evidence for a TNF-alpha-independent cytolytic mechanism. J Immunol. 1992 Jun 15;148(12):3789–3798. [PubMed] [Google Scholar]
  14. Maimone M. M., Morrison L. A., Braciale V. L., Braciale T. J. Features of target cell lysis by class I and class II MHC-restricted cytolytic T lymphocytes. J Immunol. 1986 Dec 1;137(11):3639–3643. [PubMed] [Google Scholar]
  15. Muller D., Koller B. H., Whitton J. L., LaPan K. E., Brigman K. K., Frelinger J. A. LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin-deficient mice. Science. 1992 Mar 20;255(5051):1576–1578. doi: 10.1126/science.1347959. [DOI] [PubMed] [Google Scholar]
  16. Murti K. G., Davis D. S., Kitchingman G. R. Localization of adenovirus-encoded DNA replication proteins in the nucleus by immunogold electron microscopy. J Gen Virol. 1990 Dec;71(Pt 12):2847–2857. doi: 10.1099/0022-1317-71-12-2847. [DOI] [PubMed] [Google Scholar]
  17. Ramshaw I., Ruby J., Ramsay A., Ada G., Karupiah G. Expression of cytokines by recombinant vaccinia viruses: a model for studying cytokines in virus infections in vivo. Immunol Rev. 1992 Jun;127:157–182. doi: 10.1111/j.1600-065x.1992.tb01413.x. [DOI] [PubMed] [Google Scholar]
  18. Ruddle N. H., Bergman C. M., McGrath K. M., Lingenheld E. G., Grunnet M. L., Padula S. J., Clark R. B. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med. 1990 Oct 1;172(4):1193–1200. doi: 10.1084/jem.172.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scherle P. A., Palladino G., Gerhard W. Mice can recover from pulmonary influenza virus infection in the absence of class I-restricted cytotoxic T cells. J Immunol. 1992 Jan 1;148(1):212–217. [PubMed] [Google Scholar]
  20. Sheehan K. C., Ruddle N. H., Schreiber R. D. Generation and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors. J Immunol. 1989 Jun 1;142(11):3884–3893. [PubMed] [Google Scholar]
  21. Spriggs M. K., Koller B. H., Sato T., Morrissey P. J., Fanslow W. C., Smithies O., Voice R. F., Widmer M. B., Maliszewski C. R. Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6070–6074. doi: 10.1073/pnas.89.13.6070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]
  23. Zijlstra M., Auchincloss H., Jr, Loring J. M., Chase C. M., Russell P. S., Jaenisch R. Skin graft rejection by beta 2-microglobulin-deficient mice. J Exp Med. 1992 Apr 1;175(4):885–893. doi: 10.1084/jem.175.4.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Zijlstra M., Bix M., Simister N. E., Loring J. M., Raulet D. H., Jaenisch R. Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells. Nature. 1990 Apr 19;344(6268):742–746. doi: 10.1038/344742a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES