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. 1980 Mar;27(3):767–776. doi: 10.1128/iai.27.3.767-776.1980

Role of specific cytotoxic lymphocytes in cellular immunity against murine cytomegalovirus.

M Ho
PMCID: PMC550838  PMID: 6247279

Abstract

Cytotoxic lymphocytes were generated in vitro against murine cytomegalovirus (MCMV)-infected cells by incubation with ultraviolet light-irradiated, infected fibroblasts. When passively transferred, they reduced virus titers in spleens of mice 1 day after infection with MCMV. Protection was abrogated by anti-theta serum and complement. Spleen cells from mice infected for 6 to 14 days protected mice better than cells from mice after infection for 1, 3, or 30 days. Protection by in vitro- and in vivo-generated cells was H-2K or H-2D restricted. Specific cytotoxic T lymphocytes are therefore present and operative during acute MCMV infection. However, MCMV infection inhibited the development of primary cytotoxic response against ectromelia virus. It also suppressed the ability of lymphocytes from mice with established memory for ectromelia to develop secondary cytotoxic cells in vitro, and it inhibited the development of memory cells for the cytotoxic response to ectromelia virus. In view of these data and the inability of animals recovering from MCMV infection to eliminate all infected cells, the cytotoxic response to MCMV may be qualitatively or quantitatively deficient.

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Selected References

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

  1. Araullo-Cruz T. P., Ho M., Armstrong J. A. Protective effect of early serum from mice after cytomegalovirus infection. Infect Immun. 1978 Sep;21(3):840–842. doi: 10.1128/iai.21.3.840-842.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevan M. J. Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med. 1976 May 1;143(5):1283–1288. doi: 10.1084/jem.143.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blanden R. V., Bowern N. A., Pang T. E., Gardner I. D., Parish C. R. Effects of thymus-independent (B) cells and the H-2 gene complex on antiviral function of immune thymus-derived (T) cells. Aust J Exp Biol Med Sci. 1975 Jun;53(3):187–195. doi: 10.1038/icb.1975.19. [DOI] [PubMed] [Google Scholar]
  4. Blanden R. V., Gardner I. D. The cell-mediated immune response to ectromelia virus infection. I. Kinetics and characteristics of the primary effector T cell response in vivo. Cell Immunol. 1976 Mar 15;22(2):271–282. doi: 10.1016/0008-8749(76)90029-0. [DOI] [PubMed] [Google Scholar]
  5. Blanden R. V. T cell response to viral and bacterial infection. Transplant Rev. 1974;19(0):56–88. doi: 10.1111/j.1600-065x.1974.tb00128.x. [DOI] [PubMed] [Google Scholar]
  6. Chatterjee S. N., Fiala M., Weiner J., Stewart J. A., Stacey B., Warmer N. Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients. JAMA. 1978 Nov 24;240(22):2446–2449. [PubMed] [Google Scholar]
  7. 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]
  8. Dowling J. N., Wu B. C., Armstrong J. A., Ho M. Enhancement of murine cytomegalovirus infection during graft-vs.-host reaction. J Infect Dis. 1977 Jun;135(6):990–994. doi: 10.1093/infdis/135.6.990. [DOI] [PubMed] [Google Scholar]
  9. Gardner I., Bowern N. A., Blanden R. V. Cell-mediated cytotoxicity against ectromelia virus-infected target cells. I. Specificity and kinetics. Eur J Immunol. 1974 Feb;4(2):63–67. doi: 10.1002/eji.1830040202. [DOI] [PubMed] [Google Scholar]
  10. Ho M., Ashman R. B. Development in vitro of cytotoxic lymphocytes against murine cytomegalovirus. Aust J Exp Biol Med Sci. 1979 Aug;57(4):425–428. doi: 10.1038/icb.1979.42. [DOI] [PubMed] [Google Scholar]
  11. Ho M. Cytomegalovirus infections and diseases. Dis Mon. 1978 Sep;24(12):1–61. doi: 10.1016/s0011-5029(78)80014-5. [DOI] [PubMed] [Google Scholar]
  12. Ho M. Virus infections after transplantation in man. Brief review. Arch Virol. 1977;55(1-2):1–24. doi: 10.1007/BF01314475. [DOI] [PubMed] [Google Scholar]
  13. Howard R. J., Mattsson D. M., Seidel M. V., Balfour H. H., Jr Cell-mediated immunity to murine cytomegalovirus. J Infect Dis. 1978 Nov;138(5):567–604. [PubMed] [Google Scholar]
  14. Howard R. J., Miller J., Najarian J. S. Cytomegalovirus-induced immune suppression. II. Cell-mediated immunity. Clin Exp Immunol. 1974 Sep;18(1):119–126. [PMC free article] [PubMed] [Google Scholar]
  15. Hudson J. B., Loh L., Misra V., Judd B., Suzuki J. Multiple interactions between murine cytomegalovirus and lymphoid cells in vitro. J Gen Virol. 1978 Jan;38(1):149–159. doi: 10.1099/0022-1317-38-1-149. [DOI] [PubMed] [Google Scholar]
  16. Kees U., Blanden R. V. A single genetic element in H-2K affects mouse T-cell antiviral function in poxvirus infection. J Exp Med. 1976 Feb 1;143(2):450–455. doi: 10.1084/jem.143.2.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kees U., Blanden R. V. Protective activity of secondary effector T cells generated in vitro against ectromelia virus infection in vivo. Clin Exp Immunol. 1977 Dec;30(3):338–346. [PMC free article] [PubMed] [Google Scholar]
  18. Kelsey D. K., Overall J. C., Jr, Glasgow L. A. Correlation of the suppression of mitogen responsiveness and the mixed lymphocyte reaction with the proliferative response to viral antigen of splenic lymphocytes from cytomegalovirus-infected mice. J Immunol. 1978 Aug;121(2):464–470. [PubMed] [Google Scholar]
  19. LEVINE S. EFFECT OF X-IRRADIATION ON THE RESPONSE OF ANIMAL CELLS TO VIRUS. Prog Med Virol. 1963;5:127–168. [PubMed] [Google Scholar]
  20. Lafferty K. J., Misko I. S., Cooley M. A. Allogeneic stimulation modulates the in vitro response of T cells to transplantation antigen. Nature. 1974 May 17;249(454):275–276. doi: 10.1038/249275a0. [DOI] [PubMed] [Google Scholar]
  21. Mims C. A., Gould J. The role of macrophages in mice infected with murine cytomegalovirus. J Gen Virol. 1978 Oct;41(1):143–153. doi: 10.1099/0022-1317-41-1-143. [DOI] [PubMed] [Google Scholar]
  22. Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. 3. N Engl J Med. 1973 Oct 11;289(15):781–789. doi: 10.1056/NEJM197310112891505. [DOI] [PubMed] [Google Scholar]
  23. Olding L. B., Jensen F. C., Oldstone M. B. Pathogenesis of of cytomegalovirus infection. I. Activation of virus from bone marrow-derived lymphocytes by in vitro allogenic reaction. J Exp Med. 1975 Mar 1;141(3):561–572. doi: 10.1084/jem.141.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Osborn J. E., Blazkovec A. A., Walker D. L. Immunosuppression during acute murine cytomegalovirus infection. J Immunol. 1968 Apr;100(4):835–844. [PubMed] [Google Scholar]
  25. Osborn J. E., Medearis D. N., Jr Suppression of interferon and antibody and multiplication of Newcastle disease virus in cytomegalovirus infected mice. Proc Soc Exp Biol Med. 1967 Feb;124(2):347–353. doi: 10.3181/00379727-124-31740. [DOI] [PubMed] [Google Scholar]
  26. Osborn J. E., Walker D. L. Enhancement of infectivity of murine cytomegalovirus in vitro by centrifugal inoculation. J Virol. 1968 Sep;2(9):853–858. doi: 10.1128/jvi.2.9.853-858.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pang T., Blanden R. V. Genetic factors in the stimulation of T cell responses against ectromelia virus-infected cells: role of H-2K, H-2D, and H-2I genes. Aust J Exp Biol Med Sci. 1977 Oct;55(5):549–559. doi: 10.1038/icb.1977.54. [DOI] [PubMed] [Google Scholar]
  28. Pang T., Blanden R. V. Requirements for stimulation of T cell responses against virus-infected cells: nature of ectromelia virus-infected cells capable of stimulating cytotoxic T cells in a secondary response in vitro. Aust J Exp Biol Med Sci. 1977 Oct;55(5):539–547. doi: 10.1038/icb.1977.53. [DOI] [PubMed] [Google Scholar]
  29. Pang T., Blanden R. V. The cell-mediated immune response to ectromelia virus infection. Secondary response in vitro: specificity, nature of effector and responder cells and requirements for induction of antigenic changes in stimulator cells. Aust J Exp Biol Med Sci. 1976 Jun;54(3):253–264. [PubMed] [Google Scholar]
  30. 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]
  31. Quinnan G. V., Manischewitz J. E., Ennis F. A. Cytotoxic T lymphocyte response to murine cytomegalovirus infection. Nature. 1978 Jun 15;273(5663):541–543. doi: 10.1038/273541a0. [DOI] [PubMed] [Google Scholar]
  32. Selgrade M. K., Ahmed A., Sell K. W., Gershwin M. E., Steinberg A. D. Effect of murine cytomegalovirus on the in vitro responses of T and B cells to mitogens. J Immunol. 1976 May;116(5):1459–1465. [PubMed] [Google Scholar]
  33. Starr S. E., Allison A. C. Role of T lymphocytes in recovery from murine cytomegalovirus infection. Infect Immun. 1977 Aug;17(2):458–462. doi: 10.1128/iai.17.2.458-462.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wu B. C., Dowling J. N., Armstrong J. A., Ho M. Enhancement of mouse cytomegalovirus infection during host-versus-graft reaction. Science. 1975 Oct 3;190(4209):56–58. doi: 10.1126/science.170676. [DOI] [PubMed] [Google Scholar]
  35. Wu B. C., Ho M. Characteristics of infection of B and T lymphocytes from mice after inoculation with cytomegalovirus. Infect Immun. 1979 Jun;24(3):856–864. doi: 10.1128/iai.24.3.856-864.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. 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]

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