Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Sep 1;160(3):814–826. doi: 10.1084/jem.160.3.814

In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific

PMCID: PMC2187390  PMID: 6206190

Abstract

Cloned lines of murine cytotoxic T lymphocytes (CTL) directed to type A influenza virus confer complete protection upon adoptive transfer to syngeneic mice lethally infected by influenza virus. The exquisite specificity exhibited by a subtype-specific cloned CTL in culture is reflected in its capacity to eliminate pulmonary virus and mediate recovery only in those mice infected by the virus subtype recognized by this cloned line in vitro. A cross-reactive CTL cloned line protects mice infected by either of two influenza virus subtypes. In mice dually infected with two virus subtypes, the subtype-specific CTL clone only reduces lung virus levels of the recognized virus subtype and cannot prevent these mice from dying. In contrast, adoptive transfer of the cross-reactive CTL clone into mice simultaneously infected with two virus subtypes results in reduction of pulmonary titers of both subtypes and promotes complete recovery. These results directly implicate CTL as an important antiviral defense mechanism in experimental influenza infection. In addition, these results indicate that both the induction and expression of antiviral effector activity by CTL in vivo is highly specific and therefore favor the concept that CTL express their antiviral effect in vivo by direct cytolysis of infected cells.

Full Text

The Full Text of this article is available as a PDF (834.7 KB).

Selected References

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

  1. Braciale T. J., Andrew M. E., Braciale V. L. Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes. J Exp Med. 1981 Apr 1;153(4):910–923. doi: 10.1084/jem.153.4.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braciale T. J. Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes. Cell Immunol. 1977 Oct;33(2):423–436. doi: 10.1016/0008-8749(77)90170-8. [DOI] [PubMed] [Google Scholar]
  3. Braciale T. J. Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells. J Exp Med. 1977 Sep 1;146(3):673–689. doi: 10.1084/jem.146.3.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bukowski J. F., Woda B. A., Habu S., Okumura K., Welsh R. M. Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immunol. 1983 Sep;131(3):1531–1538. [PubMed] [Google Scholar]
  5. Davidson W. F., Parish C. R. A procedure for removing red cells and dead cells from lymphoid cell suspensions. J Immunol Methods. 1975 Jun;7(2-3):291–300. doi: 10.1016/0022-1759(75)90026-5. [DOI] [PubMed] [Google Scholar]
  6. Engers H. D., Glasebrook A. L., Sorenson G. D. Allogeneic tumor rejection induced by the intravenous injection of Lyt-2+ cytolytic T lymphocyte clones. J Exp Med. 1982 Oct 1;156(4):1280–1285. doi: 10.1084/jem.156.4.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Glasebrook A. L., Kelso A., MacDonald H. R. Cytolytic T lymphocyte clones that proliferate autonomously to specific alloantigenic stimulation. II. Relationship of the Lyt-2 molecular complex to cytolytic activity, proliferation, and lymphokine secretion. J Immunol. 1983 Apr;130(4):1545–1551. [PubMed] [Google Scholar]
  8. Klein J. R., Raulet D. H., Pasternack M. S., Bevan M. J. Cytotoxic T lymphocytes produce immune interferon in response to antigen or mitogen. J Exp Med. 1982 Apr 1;155(4):1198–1203. doi: 10.1084/jem.155.4.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lin Y. L., Askonas B. A. Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions. J Exp Med. 1981 Aug 1;154(2):225–234. doi: 10.1084/jem.154.2.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lotze M. T., Line B. R., Mathisen D. J., Rosenberg S. A. The in vivo distribution of autologous human and murine lymphoid cells grown in T cell growth factor (TCGF): implications for the adoptive immunotherapy of tumors. J Immunol. 1980 Oct;125(4):1487–1493. [PubMed] [Google Scholar]
  11. Morris A. G., Lin Y. L., Askonas B. A. Immune interferon release when a cloned cytotoxic T-cell line meets its correct influenza-infected target cell. Nature. 1982 Jan 14;295(5845):150–152. doi: 10.1038/295150a0. [DOI] [PubMed] [Google Scholar]
  12. Prystowsky M. B., Ely J. M., Beller D. I., Eisenberg L., Goldman J., Goldman M., Goldwasser E., Ihle J., Quintans J., Remold H. Alloreactive cloned T cell lines. VI. Multiple lymphokine activities secreted by helper and cytolytic cloned T lymphocytes. J Immunol. 1982 Dec;129(6):2337–2344. [PubMed] [Google Scholar]
  13. Shellam G. R., Allan J. E., Papadimitriou J. M., Bancroft G. J. Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5104–5108. doi: 10.1073/pnas.78.8.5104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Taylor P. M., Askonas B. A. Diversity in the biological properties of anti-influenza cytotoxic T cell clones. Eur J Immunol. 1983 Sep;13(9):707–711. doi: 10.1002/eji.1830130904. [DOI] [PubMed] [Google Scholar]
  15. Wells M. A., Albrecht P., Ennis F. A. Recovery from a viral respiratory infection. I. Influenza pneumonia in normal and T-deficient mice. J Immunol. 1981 Mar;126(3):1036–1041. [PubMed] [Google Scholar]
  16. Wells M. A., Ennis F. A., Albrecht P. Recovery from a viral respiratory infection. II. Passive transfer of immune spleen cells to mice with influenza pneumonia. J Immunol. 1981 Mar;126(3):1042–1046. [PubMed] [Google Scholar]
  17. Widmer M. B., Bach F. H. Antigen-driven helper cell-independent cloned cytolytic T lymphocytes. Nature. 1981 Dec 24;294(5843):750–752. doi: 10.1038/294750a0. [DOI] [PubMed] [Google Scholar]
  18. Yap K. L., Ada G. L. Cytotoxic T cells in the lungs of mice infected with an influenza A virus. Scand J Immunol. 1978;7(1):73–80. doi: 10.1111/j.1365-3083.1978.tb00428.x. [DOI] [PubMed] [Google Scholar]
  19. Yap K. L., Ada G. L., McKenzie I. F. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. doi: 10.1038/273238a0. [DOI] [PubMed] [Google Scholar]
  20. Yap K. L., Ada G. L. The recovery of mice from influenza virus infection: adoptive transfer of immunity with immune T lymphocytes. Scand J Immunol. 1978;7(5):389–397. doi: 10.1111/j.1365-3083.1978.tb00469.x. [DOI] [PubMed] [Google Scholar]
  21. Yap K. L., Braciale T. J., Ada G. L. Role of T-cell function in recovery from murine influenza infection. Cell Immunol. 1979 Mar 15;43(2):341–351. doi: 10.1016/0008-8749(79)90178-3. [DOI] [PubMed] [Google Scholar]
  22. Zinkernagel R. M., Althage A. Antiviral protection by virus-immune cytotoxic T cells: infected target cells are lysed before infectious virus progeny is assembled. J Exp Med. 1977 Mar 1;145(3):644–651. doi: 10.1084/jem.145.3.644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zinkernagel R. M., Welsh R. M. H-2 compatibility requirement for virus-specific T cell-mediated effector functions in vivo. I. Specificity of T cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H-2K and H-2D. J Immunol. 1976 Nov;117(5 Pt 1):1495–1502. [PubMed] [Google Scholar]

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

RESOURCES