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. 1980 Apr 1;151(4):815–826. doi: 10.1084/jem.151.4.815

Specificity, Ly phenotype, and H-2 compatibility requirements of effector cells in delayed-type hypersensitivity responses to murine influenza virus infection

PMCID: PMC2185830  PMID: 6966309

Abstract

Delayed-type hypersensitivity (DTH) to infectious and to noninfectious (UV-irradiated) influenza A viral preparations was measured in mice by the increase in footpad swelling 24 h after injection of the eliciting virus. DTH mice sensitized with noninfectious virus was elicited only by virus that shared hemagglutinin specificity with the sensitizing virus, whereas footpad injection of a given A-strain virus (A/WSN) could elicit DTH in mice sensitized with a variety of infectious A- strain viruses, including some not sharing hemagglutinin or neuraminidase specificities. The effector T cells generated in mice sensitized with either form of virus were sensitive to anti-Ly 1.1 serum and complement, but not to anti-Ly 2.1 serum and complement. Adoptive transfer of DTH was H-2 restricted. With spleen cells from mice sensitized subcutaneously with either infectious or noninfectious virus, sharing of the IA region was both necessary and sufficient for successful transfer to occur. Cells recovered from infected mouse lungs, and secondary effector cells generated in vitro transferred DTH if injected into the footpad with the eliciting virus. The effector cells had the Ly 1 phenotype, and, in both cases, the cells were I restricted. These results contrast with earlier findings that transfer of DTH to lymphocytic choriomeningitis virus infection required K- or D- region sharing between donor and recipient. Thus, the earlier hypothesis that multiplying infectious agents such as viruses would "alter" K- or D-coded, rather than I-coded, structures is not generally correct.

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Selected References

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

  1. Asherson G. L., Mayhew B., Perera M. A. The production of contact sensitivity by the injection into the footpads of recipients of the lymph node cells from mice 1 day after painting the skin with contact sensitizing agent: requirement for matching at the major histocompatibility complex between donor and recipient mice. Immunology. 1979 May;37(1):241–245. [PMC free article] [PubMed] [Google Scholar]
  2. Beverley P. C., Woody J., Dunkley M., Feldmann M., McKenzie I. Separation of suppressor and killer T cells by surgace phenotype. Nature. 1976 Aug 5;262(5568):495–497. doi: 10.1038/262495a0. [DOI] [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. Specificity of cytotoxicity T cells directed to influenza virus hemagglutinin. J Exp Med. 1979 Apr 1;149(4):856–869. doi: 10.1084/jem.149.4.856. [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. Cooper M. G. Delayed-type hypersensitivity in the mouse. I. Induction and elicitation by Salmonella adelaide flagellin and its derivatives. Scand J Immunol. 1972;1(2):167–178. doi: 10.1111/j.1365-3083.1972.tb00596.x. [DOI] [PubMed] [Google Scholar]
  7. Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Floc'h F., Werner G. H. Heterotypic protective immune reactions in mice infected with distinct serotypes of human influenza virus. Ann Microbiol (Paris) 1978 May-Jun;129(4):509–524. [PubMed] [Google Scholar]
  10. Hudson B. W., Wolff K., DeMartini J. C. Delayed-type hypersensitivity responses in mice infected with St. Louis encephalitis virus: kinetics of the response and effects of immunoregulatory agents. Infect Immun. 1979 Apr;24(1):71–76. doi: 10.1128/iai.24.1.71-76.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kraaijeveld C. A., Harmsen M., Khader Boutahar-Trouw B. Delayed-type hypersensitivity against Semliki Forest virus in mice. Infect Immun. 1979 Feb;23(2):219–223. doi: 10.1128/iai.23.2.219-223.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lagrange P. H., Tsiang H., Hurtrel B., Ravisse P. Delayed-type hypersensitivity to rabies virus in mice: assay of active or passive sensitization by the footpad test. Infect Immun. 1978 Sep;21(3):931–939. doi: 10.1128/iai.21.3.931-939.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Miller J. F., Vadas M. A., Whitelaw A., Gamble J. H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5095–5098. doi: 10.1073/pnas.72.12.5095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pang T., McKenzie I. F., Blanden R. V. Cooperation between mouse T-cell subpopulations in the cell-mediated response to a natural poxvirus pathogen. Cell Immunol. 1976 Oct;26(2):153–159. doi: 10.1016/0008-8749(76)90359-2. [DOI] [PubMed] [Google Scholar]
  15. Peters R. L., Donahoe R. M., Kelloff G. J. Assay in the mouse for delayed-type hypersensitivity to murine leukemia virus. J Natl Cancer Inst. 1975 Nov;55(5):1089–1095. doi: 10.1093/jnci/55.5.1089. [DOI] [PubMed] [Google Scholar]
  16. Tosolini F. A., Mims C. A. Effect of murine strain and viral strain on the pathogenesis of lymphocytic choriomeningitis infection and a study of footpad responses. J Infect Dis. 1971 Feb;123(2):134–144. doi: 10.1093/infdis/123.2.134. [DOI] [PubMed] [Google Scholar]
  17. Vadas M. A., Miller J. F., Gamble J., Whitelaw A. A radioisotopic method to measure delayed type hypersensitivity in the mouse. I. Studies in sensitized and normal mice. Int Arch Allergy Appl Immunol. 1975;49(5):670–692. doi: 10.1159/000231449. [DOI] [PubMed] [Google Scholar]
  18. Vadas M. A., Miller J. F., McKenzie I. F., Chism S. E., Shen F. W., Boyse E. A., Gamble J. R., Whitelaw A. M. Ly and Ia antigen phenotypes of T cells involved in delayed-type hypersensitivity and in suppression. J Exp Med. 1976 Jul 1;144(1):10–19. doi: 10.1084/jem.144.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weinberger J. Z., Greene M. I., Benacerraf B., Dorf M. E. Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. I. Genetic control of delayed-type hypersensitivity by VH and I-A-region genes. J Exp Med. 1979 Jun 1;149(6):1336–1348. doi: 10.1084/jem.149.6.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Yap K. L., Ada G. L. Cytotoxic T cells specific for influenza virus-infected target cells. Immunology. 1977 Feb;32(2):151–159. [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. 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]
  25. Zinkernagel R. M. H-2 restriction of virus-specific T-cell-mediated effector functions in vivo. II. Adoptive transfer of delayed-type hypersensitivity to murine lymphocytic choriomeningits virus is restriced by the K and D region of H-2. J Exp Med. 1976 Sep 1;144(3):776–787. doi: 10.1084/jem.144.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. 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]

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