Abstract
The experiments described establish that CD4+ T-cell-dependent effector mechanisms can eliminate an H3N2 influenza A virus from lung cells that are unable to express class II major histocompatibility complex (MHC) glycoproteins. Radiation chimeras were made by using CD4+ T cells and bone marrow from CD8-depleted, MHC class II +/+ mice and irradiated (950 rads) MHC class II -/- recipients. The influenza virus-specific CD4+ T-cell responses in these +/+-->-/- mice were not obviously different from those in the +/+-->+/+ controls: the cytokine profiles, the spectra of plasma cells producing the various immunoglobulin isotypes, and the frequencies of virus-specific CD4+ T cells were similar for the two groups. Expression of class II MHC glycoproteins on stimulator cells, B lymphocytes, and monocytes/macrophages is apparently sufficient for CD4+ T cells to terminate influenza virus infection of MHC class II -/- respiratory epithelium. A possible explanation is that the local spread of this lytic virus in the lung is limited by cytokines and/or antibody.
Full Text
The Full Text of this article is available as a PDF (184.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akira S., Taga T., Kishimoto T. Interleukin-6 in biology and medicine. Adv Immunol. 1993;54:1–78. doi: 10.1016/s0065-2776(08)60532-5. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Bix M., Raulet D. Inefficient positive selection of T cells directed by haematopoietic cells. Nature. 1992 Sep 24;359(6393):330–333. doi: 10.1038/359330a0. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Ceredig R., Allan J. E. Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology. Clin Immunol Immunopathol. 1988 Apr;47(1):19–26. doi: 10.1016/0090-1229(88)90141-9. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Hou S., Southern P. J. Lymphocytic choriomeningitis virus induces a chronic wasting disease in mice lacking class I major histocompatibility complex glycoproteins. J Neuroimmunol. 1993 Jul;46(1-2):11–17. doi: 10.1016/0165-5728(93)90228-q. [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]
- Ewing C., Topham D. J., Doherty P. C. Prevalence and activation phenotype of Sendai virus-specific CD4+ T cells. Virology. 1995 Jun 20;210(1):179–185. doi: 10.1006/viro.1995.1329. [DOI] [PubMed] [Google Scholar]
- Fujihashi K., McGhee J. R., Beagley K. W., McPherson D. T., McPherson S. A., Huang C. M., Kiyono H. Cytokine-specific ELISPOT assay. Single cell analysis of IL-2, IL-4 and IL-6 producing cells. J Immunol Methods. 1993 Apr 2;160(2):181–189. doi: 10.1016/0022-1759(93)90176-8. [DOI] [PubMed] [Google Scholar]
- Fung-Leung W. P., Kündig T. M., Zinkernagel R. M., Mak T. W. Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression. J Exp Med. 1991 Dec 1;174(6):1425–1429. doi: 10.1084/jem.174.6.1425. [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]
- Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
- Horimoto T., Kawaoka Y. The hemagglutinin cleavability of a virulent avian influenza virus by subtilisin-like endoproteases is influenced by the amino acid immediately downstream of the cleavage site. Virology. 1995 Jul 10;210(2):466–470. doi: 10.1006/viro.1995.1363. [DOI] [PubMed] [Google Scholar]
- Hou S., Doherty P. C. Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus-infected epithelium. Eur J Immunol. 1995 Jan;25(1):111–116. doi: 10.1002/eji.1830250120. [DOI] [PubMed] [Google Scholar]
- Hou S., Doherty P. C. Partitioning of responder CD8+ T cells in lymph node and lung of mice with Sendai virus pneumonia by LECAM-1 and CD45RB phenotype. J Immunol. 1993 Jun 15;150(12):5494–5500. [PubMed] [Google Scholar]
- 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]
- Hou S., Fishman M., Murti K. G., Doherty P. C. Divergence between cytotoxic effector function and tumor necrosis factor alpha production for inflammatory CD4+ T cells from mice with Sendai virus pneumonia. J Virol. 1993 Oct;67(10):6299–6302. doi: 10.1128/jvi.67.10.6299-6302.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hou S., Hyland L., Ryan K. W., Portner A., Doherty P. C. Virus-specific CD8+ T-cell memory determined by clonal burst size. Nature. 1994 Jun 23;369(6482):652–654. doi: 10.1038/369652a0. [DOI] [PubMed] [Google Scholar]
- Hou S., Mo X. Y., Hyland L., Doherty P. C. Host response to Sendai virus in mice lacking class II major histocompatibility complex glycoproteins. J Virol. 1995 Mar;69(3):1429–1434. doi: 10.1128/jvi.69.3.1429-1434.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hyland L., Sangster M., Sealy R., Coleclough C. Respiratory virus infection of mice provokes a permanent humoral immune response. J Virol. 1994 Sep;68(9):6083–6086. doi: 10.1128/jvi.68.9.6083-6086.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Markowitz J. S., Auchincloss H., Jr, Grusby M. J., Glimcher L. H. Class II-positive hematopoietic cells cannot mediate positive selection of CD4+ T lymphocytes in class II-deficient mice. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2779–2783. doi: 10.1073/pnas.90.7.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mo X. Y., Sarawar S. R., Doherty P. C. Induction of cytokines in mice with parainfluenza pneumonia. J Virol. 1995 Feb;69(2):1288–1291. doi: 10.1128/jvi.69.2.1288-1291.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Palladino G., Mozdzanowska K., Washko G., Gerhard W. Virus-neutralizing antibodies of immunoglobulin G (IgG) but not of IgM or IgA isotypes can cure influenza virus pneumonia in SCID mice. J Virol. 1995 Apr;69(4):2075–2081. doi: 10.1128/jvi.69.4.2075-2081.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sangster M., Hyland L., Sealy R., Coleclough C. Distinctive kinetics of the antibody-forming cell response to Sendai virus infection of mice in different anatomical compartments. Virology. 1995 Feb 20;207(1):287–291. doi: 10.1006/viro.1995.1079. [DOI] [PubMed] [Google Scholar]
- Sarawar S. R., Carding S. R., Allan W., McMickle A., Fujihashi K., Kiyono H., McGhee J. R., Doherty P. C. Cytokine profiles of bronchoalveolar lavage cells from mice with influenza pneumonia: consequences of CD4+ and CD8+ T cell depletion. Reg Immunol. 1993 May-Aug;5(3-4):142–150. [PubMed] [Google Scholar]
- Sarawar S. R., Doherty P. C. Concurrent production of interleukin-2, interleukin-10, and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. J Virol. 1994 May;68(5):3112–3119. doi: 10.1128/jvi.68.5.3112-3119.1994. [DOI] [PMC free article] [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]
- 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]
- Tripp R. A., Hou S., McMickle A., Houston J., Doherty P. C. Recruitment and proliferation of CD8+ T cells in respiratory virus infections. J Immunol. 1995 Jun 1;154(11):6013–6021. [PubMed] [Google Scholar]
- Walker J. A., Sakaguchi T., Matsuda Y., Yoshida T., Kawaoka Y. Location and character of the cellular enzyme that cleaves the hemagglutinin of a virulent avian influenza virus. Virology. 1992 Sep;190(1):278–287. doi: 10.1016/0042-6822(92)91214-f. [DOI] [PubMed] [Google Scholar]