Abstract
We investigated the role of different lymphocyte subpopulations in the host defense reaction against influenza virus infection, taking advantage of various immunodeficient mouse strains. Whereas, following immunization, wild-type animals showed complete protection against challenge with a lethal dose of A/PR8/34 (PR8) virus, mice that lack both B and T cells but not NK cells (namely, scid and RAG2(-/-) mice) did not display any protective effect in similar conditions. By contrast, J(H)D(-/-) mice devoid of B cells and immunized with virus showed a protective response after challenge with a lethal dose. The immunized J(H)D(-/-) mice that survived completely recovered from the influenza virus infection. Immunized J(H)D(-/+) mice exhibited a more complete protection, suggesting the role of specific antibodies in resistance to infection. To assess the role of natural immunity in the host defense against influenza virus, we carried out experiments with scid mice challenged with lower but still lethal doses of PR8 virus. While an increased NK activity and an increased number of NK1.1+ cells in lungs of scid mice infected with PR8 virus were noted, in vivo depletion of the NK1.1+ cells did not affect the overall survival of the mice. Our results show that specific T cells mediate protection and recovery of J(H)D(-/-) mice immunized with live virus and challenged with lethal doses of influenza virus.
Full Text
The Full Text of this article is available as a PDF (215.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ada G. L., Jones P. D. The immune response to influenza infection. Curr Top Microbiol Immunol. 1986;128:1–54. doi: 10.1007/978-3-642-71272-2_1. [DOI] [PubMed] [Google Scholar]
- Alt F. W., Rathbun G., Oltz E., Taccioli G., Shinkai Y. Function and control of recombination-activating gene activity. Ann N Y Acad Sci. 1992 May 4;651:277–294. doi: 10.1111/j.1749-6632.1992.tb24626.x. [DOI] [PubMed] [Google Scholar]
- Blunt T., Finnie N. J., Taccioli G. E., Smith G. C., Demengeot J., Gottlieb T. M., Mizuta R., Varghese A. J., Alt F. W., Jeggo P. A. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell. 1995 Mar 10;80(5):813–823. doi: 10.1016/0092-8674(95)90360-7. [DOI] [PubMed] [Google Scholar]
- Bodmer H., Obert G., Chan S., Benoist C., Mathis D. Environmental modulation of the autonomy of cytotoxic T lymphocytes. Eur J Immunol. 1993 Jul;23(7):1649–1654. doi: 10.1002/eji.1830230738. [DOI] [PubMed] [Google Scholar]
- Burns W., Billups L. C., Notkins A. L. Thymus dependence of viral antigens. Nature. 1975 Aug 21;256(5519):654–656. doi: 10.1038/256654a0. [DOI] [PubMed] [Google Scholar]
- Carding S. R., Allan W., McMickle A., Doherty P. C. Activation of cytokine genes in T cells during primary and secondary murine influenza pneumonia. J Exp Med. 1993 Feb 1;177(2):475–482. doi: 10.1084/jem.177.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carroll A. M., Hardy R. R., Bosma M. J. Occurrence of mature B (IgM+, B220+) and T (CD3+) lymphocytes in scid mice. J Immunol. 1989 Aug 15;143(4):1087–1093. [PubMed] [Google Scholar]
- Chen J., Trounstine M., Alt F. W., Young F., Kurahara C., Loring J. F., Huszar D. Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. Int Immunol. 1993 Jun;5(6):647–656. doi: 10.1093/intimm/5.6.647. [DOI] [PubMed] [Google Scholar]
- 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]
- Ennis F. A., Wells M. A., Butchko G. M., Albrecht P. Evidence that cytotoxic T cells are part of the host's response to influenza pneumonia. J Exp Med. 1978 Nov 1;148(5):1241–1250. doi: 10.1084/jem.148.5.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Epstein M. M., Di Rosa F., Jankovic D., Sher A., Matzinger P. Successful T cell priming in B cell-deficient mice. J Exp Med. 1995 Oct 1;182(4):915–922. doi: 10.1084/jem.182.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham M. B., Braciale V. L., Braciale T. J. Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection. J Exp Med. 1994 Oct 1;180(4):1273–1282. doi: 10.1084/jem.180.4.1273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isobe H., Alt F., Bona C. A., Schulman J. Intact antiinfluenza virus immune response in targeted kappa-deficient mice. Viral Immunol. 1994;7(1):25–30. doi: 10.1089/vim.1994.7.25. [DOI] [PubMed] [Google Scholar]
- Kris R. M., Yetter R. A., Cogliano R., Ramphal R., Small P. A. Passive serum antibody causes temporary recovery from influenza virus infection of the nose, trachea and lung of nude mice. Immunology. 1988 Mar;63(3):349–353. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Lucas S. J., Barry D. W., Kind P. Antibody production and protection against influenza virus in immunodeficient mice. Infect Immun. 1978 Apr;20(1):115–119. doi: 10.1128/iai.20.1.115-119.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lukacher A. E., Braciale V. L., Braciale T. J. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 1;160(3):814–826. doi: 10.1084/jem.160.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackenzie C. D., Taylor P. M., Askonas B. A. Rapid recovery of lung histology correlates with clearance of influenza virus by specific CD8+ cytotoxic T cells. Immunology. 1989 Jul;67(3):375–381. [PMC free article] [PubMed] [Google Scholar]
- Nonacs R., Humborg C., Tam J. P., Steinman R. M. Mechanisms of mouse spleen dendritic cell function in the generation of influenza-specific, cytolytic T lymphocytes. J Exp Med. 1992 Aug 1;176(2):519–529. doi: 10.1084/jem.176.2.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Puck J. M., Glezen W. P., Frank A. L., Six H. R. Protection of infants from infection with influenza A virus by transplacentally acquired antibody. J Infect Dis. 1980 Dec;142(6):844–849. doi: 10.1093/infdis/142.6.844. [DOI] [PubMed] [Google Scholar]
- 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]
- Stein-Streilein J., Bennett M., Mann D., Kumar V. Natural killer cells in mouse lung: surface phenotype, target preference, and response to local influenza virus infection. J Immunol. 1983 Dec;131(6):2699–2704. [PubMed] [Google Scholar]
- Sullivan J. L., Mayner R. E., Barry D. W., Ennis F. A. Influenza virus infection in nude mice. J Infect Dis. 1976 Jan;133(1):91–94. doi: 10.1093/infdis/133.1.91. [DOI] [PubMed] [Google Scholar]
- Taylor P. M., Askonas B. A. Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology. 1986 Jul;58(3):417–420. [PMC free article] [PubMed] [Google Scholar]
- Virelizier J. L. Host defenses against influenza virus: the role of anti-hemagglutinin antibody. J Immunol. 1975 Aug;115(2):434–439. [PubMed] [Google Scholar]
- 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]
- 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]