Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1980 Jun;28(3):799–811. doi: 10.1128/iai.28.3.799-811.1980

Induction of cytolytic T- and B-cell responses against influenza virus infections.

D Armerding, H Rossiter
PMCID: PMC551021  PMID: 6967451

Abstract

Inoculation of mice with live influenza virus results in the induction of cytotoxic thymus-derived (T) lymphocytes and of bone marrow-derived (B) cells producing antiviral antibodies. An assay system was developed to evaluate both types of immune responses on a cellular basis within the same lymphocyte pool with no need to separate out the different effector cell classes. The test system represented a modification of the 51Cr-release assay. T-cell activity was measured exclusively in the absence of active complement using targets that were compatible for determinants encoded by the mouse major histocompatibility gene complex, H-2. H-2-different and even xenogeneic target cells were lysed in the presence of either non-inactivated fetal calf serum or normal rabbit serum as a complement source. Cytotoxicity was mediated in the latter case by direct interaction of B-cell-produced immunoglobulin directed to viral antigens expressed by the target cell and complement. Antibody-dependent cell-mediated cytotoxicity mechanisms did not contribute to cytotoxicity in the test system described. It was demontrated that the cytolytic B-cell responses of one particular strain of mice (BALB/c) against different influenza A viruses were restricted to the immunizing virus on the effector cell level. In another strain of mice (C3H), B cells revealed a broad cross-reactive response resembling that of killer T cells.

Full text

PDF
799

Selected References

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

  1. Aymard-Henry M., Coleman M. T., Dowdle W. R., Laver W. G., Schild G. C., Webster R. G. Influenzavirus neuraminidase and neuraminidase-inhibition test procedures. Bull World Health Organ. 1973;48(2):199–202. [PMC free article] [PubMed] [Google Scholar]
  2. Biddison W. E., Doherty P. C., Webster R. G. Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses. J Exp Med. 1977 Sep 1;146(3):690–697. doi: 10.1084/jem.146.3.690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Braciale T. J., Yap K. L. Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. J Exp Med. 1978 Apr 1;147(4):1236–1252. doi: 10.1084/jem.147.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brunner K. T., Mauel J., Cerottini J. C., Chapuis B. Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology. 1968 Feb;14(2):181–196. [PMC free article] [PubMed] [Google Scholar]
  7. Cancro M. P., Gerhard W., Klinman N. R. The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice. J Exp Med. 1978 Mar 1;147(3):776–787. doi: 10.1084/jem.147.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doherty P. C., Effros R. B., Bennink J. Heterogeneity of the cytotoxic response of thymus-derived lymphocytes after immunization with influenza viruses. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1209–1213. doi: 10.1073/pnas.74.3.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Doherty P. C., Zinkernagel R. M. Specific immune lysis of paramyxovirus-infected cells by H-2-compatible thymus-derived lymphocytes. Immunology. 1976 Jul;31(1):27–32. [PMC free article] [PubMed] [Google Scholar]
  10. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  11. Effros R. B., Doherty P. C., Gerhard W., Bennink J. Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses. J Exp Med. 1977 Mar 1;145(3):557–568. doi: 10.1084/jem.145.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ennis F. A., Martin W. J., Verbonitz M. W., Butchko G. M. Specificity studies on cytotoxic thymus-derived lymphocytes reactive with influenza virus-infected cells: evidence for dual recognition of H-2 and viral hemagglutinin antigens. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3006–3010. doi: 10.1073/pnas.74.7.3006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gardner I. D., Bowern N. A., Blanden R. V. Cell-medicated cytotoxicity against ectromelia virus-infected target cells. III. Role of the H-2 gene complex. Eur J Immunol. 1975 Feb;5(2):122–127. doi: 10.1002/eji.1830050210. [DOI] [PubMed] [Google Scholar]
  14. Greenberg S. B., Criswell B. S., Six H. R., Couch R. B. Lymphocyte cytotoxicity to influenza virus-infected cells. II. Requirement for antibody and non-T lymphocytes. J Immunol. 1977 Dec;119(6):2100–2106. [PubMed] [Google Scholar]
  15. Hale A. H., Witte O. N., Baltimore D., Eisen H. N. Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1978 Feb;75(2):970–974. doi: 10.1073/pnas.75.2.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  17. Katz D. H., Osborne D. P., Jr The allogeneic effect in inbred mice. II. Establishment of the cellular interactions required for enhancement of antibody production by the graft-versus-host reaction. J Exp Med. 1972 Sep 1;136(3):455–465. doi: 10.1084/jem.136.3.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kohl S., Cahall D. L., Walters D. L., Schaffner V. E. Murine antibody-dependent cellular cytotoxicity to herpes simplex virus-infected target cells. J Immunol. 1979 Jul;123(1):25–30. [PubMed] [Google Scholar]
  19. Koszinowski U., Ertl H. Cytotoxic interactions of virus specific effector cells with virus infected targets of different cell type. J Immunogenet. 1977 Apr;4(2):107–114. doi: 10.1111/j.1744-313x.1977.tb00620.x. [DOI] [PubMed] [Google Scholar]
  20. Koszinowski U., Thomssen R. Target cell-dependent T cell-mediated lysis of vaccinia virus-infected cells. Eur J Immunol. 1975 Apr;5(4):245–251. doi: 10.1002/eji.1830050405. [DOI] [PubMed] [Google Scholar]
  21. McLaren C., Grubbs G. E., Ennis F. A. Detection of cells producing surface antigen-specific antibody to influenza viruses. J Clin Microbiol. 1978 Oct;8(4):438–444. doi: 10.1128/jcm.8.4.438-444.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McMichael A. HLA restriction of human cytotoxic T lymphocytes specific for influenza virus. Poor recognition of virus associated with HLA A2. J Exp Med. 1978 Dec 1;148(6):1458–1467. doi: 10.1084/jem.148.6.1458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moroni C., Schumann G. Lipopolysaccharide induces C-type virus in short term cultures of BALB/c spleen cells. Nature. 1975 Mar 6;254(5495):60–61. doi: 10.1038/254060a0. [DOI] [PubMed] [Google Scholar]
  24. Moroni C., Schumann G., Robert-Guroff M., Suter E. R., Martin D. Induction of endogenous murine C-type virus in spleen cell cultures treated with mitogens and 5-bromo-2'-deoxyuridine. Proc Natl Acad Sci U S A. 1975 Feb;72(2):535–538. doi: 10.1073/pnas.72.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Oxford J. S., Schild G. C. Immunological and physicochemical studies of influenza matrix (M) polypeptides. Virology. 1976 Oct 15;74(2):394–402. doi: 10.1016/0042-6822(76)90345-7. [DOI] [PubMed] [Google Scholar]
  26. Pearson G. R. In vitro and in vivo investigations on antibody-dependent cellular cytotoxicity. Curr Top Microbiol Immunol. 1978;80:65–96. doi: 10.1007/978-3-642-66956-9_3. [DOI] [PubMed] [Google Scholar]
  27. Pfizenmaier K., Jung H., Starzinski-Powitz A., Röllinghoff M., Wagner H. The role of T cells in anti-herpes simplex virus immunity. I. Induction of antigen-specific cytotoxic T lymphocytes. J Immunol. 1977 Sep;119(3):939–944. [PubMed] [Google Scholar]
  28. Potter C. W., Oxford J. S. Determinants of immunity to influenza infection in man. Br Med Bull. 1979 Jan;35(1):69–75. doi: 10.1093/oxfordjournals.bmb.a071545. [DOI] [PubMed] [Google Scholar]
  29. Sethi K. K., Brandis H. Specifically immune mouse T-cells can destroy H-2 compatible murine target cells infected with herpes simplex virus types 1 or 2. Z Immunitatsforsch Immunobiol. 1977 Jul;153(2):162–173. [PubMed] [Google Scholar]
  30. Virelizier J. L., Allison A. C., Schild G. C. Immune responses to influenza virus in the mouse, and their role in control of the infection. Br Med Bull. 1979 Jan;35(1):65–68. doi: 10.1093/oxfordjournals.bmb.a071544. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Webster R. G., Hinshaw V. S. Matrix protein from influenza A virus and its role in cross-protection in mice. Infect Immun. 1977 Sep;17(3):561–566. doi: 10.1128/iai.17.3.561-566.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wecker E., Schimpl A., Hünig T. Expression of MuLV GP71-like antigen in normal mouse spleen cells induced by antigenic stimulation. Nature. 1977 Oct 13;269(5629):598–600. doi: 10.1038/269598a0. [DOI] [PubMed] [Google Scholar]
  34. Zinkernagel R. M., Doherty P. C. Immunological surveillance against altered self components by sensitised T lymphocytes in lymphocytic choriomeningitis. Nature. 1974 Oct 11;251(5475):547–548. doi: 10.1038/251547a0. [DOI] [PubMed] [Google Scholar]
  35. Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]
  36. Zinkernagel R. M. H-2 restriction of virus-specific cytotoxicity across the H-2 barrier. Separate effector T-cell specificities are associated with self-H-2 and with the tolerated allogeneic H-2 in chimeras. J Exp Med. 1976 Oct 1;144(4):933–945. doi: 10.1084/jem.144.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zweerink H. J., Askonas B. A., Millican D., Courtneidge S. A., Skehel J. J. Cytotoxic T cells to type A influenza virus; viral hemagglutinin induces A-strain specificity while infected cells confer cross-reactive cytotoxicity. Eur J Immunol. 1977 Sep;7(9):630–635. doi: 10.1002/eji.1830070910. [DOI] [PubMed] [Google Scholar]
  38. Zweerink H. J., Courtneidge S. A., Skehel J. J., Crumpton M. J., Askonas B. A. Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses. Nature. 1977 May 26;267(5609):354–356. doi: 10.1038/267354a0. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES