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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1988 Dec;74(3):326–332.

The cellular immune response to cell-associated and cell-free cytomegalovirus (CMV) antigens after primary CMV-infection in non-immunocompromised hosts: development and maintenance of CMV-latency and its influence on immunocompetence.

H W Roenhorst 1, C G Kallenberg 1, T H The 1
PMCID: PMC1542018  PMID: 2853014

Abstract

Development and maintenance of cellular immunity to cell-associated CMV-antigens (CMVFF) was investigated in non-immunocompromised hosts during the first year (group I, n = 11) and 1 to 5 years (group II, n = 9) after a symptomatic primary CMV infection, as well as in healthy CMV-seropositive controls without a history of CMV disease (group III, n = 28). During the acute phase (0-2 months) of a primary CMV-infection CMVFF-induced lymphocyte proliferation was severely decreased compared to that in the post-illness phase (5-12 months), and to that in groups II and III. After the reconvalescent period (3-4 months) it gradually increased to levels seen in group III. In group II higher responses to CMVFF were found than in group III or during the post-illness phase of a primary infection. In general CMV-virion induced lymphocyte proliferation showed the same pattern of development as the CMVFF-induced lymphocyte response, but during the acute phase (0-2 months) a lack of correlation was observed between lymphocyte proliferation to CMVFF and CMV-virions. Lymphocyte proliferation to PHA, Con A, allogeneic lymphocytes and recall antigens were severely depressed in the acute phase of a primary CMV-infection and restored gradually to levels seen in groups II and III, with the exception of Con A-reactivity. The latter response remained depressed when compared to healthy seropositive controls, not only during the post-illness period, but also later on (group II).

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Selected References

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  1. Betts R. F., Hanshaw J. B. Cytomegalovirus (CMV) in the compromised host(s). Annu Rev Med. 1977;28:103–110. doi: 10.1146/annurev.me.28.020177.000535. [DOI] [PubMed] [Google Scholar]
  2. Borysiewicz L. K., Morris S., Page J. D., Sissons J. G. Human cytomegalovirus-specific cytotoxic T lymphocytes: requirements for in vitro generation and specificity. Eur J Immunol. 1983 Oct;13(10):804–809. doi: 10.1002/eji.1830131005. [DOI] [PubMed] [Google Scholar]
  3. Carney W. P., Hirsch M. S. Mechanisms of immunosuppression in cytomegalovirus mononucleosis. II. Virus-monocyte interactions. J Infect Dis. 1981 Jul;144(1):47–54. doi: 10.1093/infdis/144.1.47. [DOI] [PubMed] [Google Scholar]
  4. Ho M. The lymphocyte in infections with Epstein-Barr virus and cytomegalovirus. J Infect Dis. 1981 Jun;143(6):857–862. doi: 10.1093/infdis/143.6.857. [DOI] [PubMed] [Google Scholar]
  5. Huang E. S., Chen S. T., Pagano J. S. Human cytomegalovirus. I. Purification and characterization of viral DNA. J Virol. 1973 Dec;12(6):1473–1481. doi: 10.1128/jvi.12.6.1473-1481.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kirchner H. Immunobiology of infection with human cytomegalovirus. Adv Cancer Res. 1983;40:31–105. doi: 10.1016/s0065-230x(08)60679-x. [DOI] [PubMed] [Google Scholar]
  7. Levin M. J., Rinaldo C. R., Jr, Leary P. L., Zaia J. A., Hirsch M. S. Immune response to herpesvirus antigens in adults with acute cytomegaloviral mononucleosis. J Infect Dis. 1979 Dec;140(6):851–857. doi: 10.1093/infdis/140.6.851. [DOI] [PubMed] [Google Scholar]
  8. Middeldorp J. M., Jongsma J., ter Haar A., Schirm J., The T. H. Detection of immunoglobulin M and G antibodies against cytomegalovirus early and late antigens by enzyme-linked immunosorbent assay. J Clin Microbiol. 1984 Oct;20(4):763–771. doi: 10.1128/jcm.20.4.763-771.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Moller-Larsen A., Andersen H. K., Heron I., Sarov I. In vitro stimulation of human lymphocytes by purified cytomegalovirus. Intervirology. 1975;6(4-5):249–257. doi: 10.1159/000149479. [DOI] [PubMed] [Google Scholar]
  10. Quinnan G. V., Ennis F. A. Cell-mediated immunity in cytomegalovirus infections--a review. Comp Immunol Microbiol Infect Dis. 1980;3(3):283–290. doi: 10.1016/0147-9571(80)90004-1. [DOI] [PubMed] [Google Scholar]
  11. Reddehase M. J., Koszinowski U. H. Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection. Nature. 1984 Nov 22;312(5992):369–371. doi: 10.1038/312369a0. [DOI] [PubMed] [Google Scholar]
  12. Rice G. P., Schrier R. D., Oldstone M. B. Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6134–6138. doi: 10.1073/pnas.81.19.6134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rinaldo C. R., Jr, Black P. H., Hirsch M. S. Interaction of cytomegalovirus with leukocytes from patients with mononucleosis due to cytomegalovirus. J Infect Dis. 1977 Nov;136(5):667–678. doi: 10.1093/infdis/136.5.667. [DOI] [PubMed] [Google Scholar]
  14. Rinaldo C. R., Jr, Carney W. P., Richter B. S., Black P. H., Hirsch M. S. Mechanisms of immunosuppression in cytomegaloviral mononucleosis. J Infect Dis. 1980 Apr;141(4):488–495. doi: 10.1093/infdis/141.4.488. [DOI] [PubMed] [Google Scholar]
  15. Rodgers B. C., Scott D. M., Mundin J., Sissons J. G. Monocyte-derived inhibitor of interleukin 1 induced by human cytomegalovirus. J Virol. 1985 Sep;55(3):527–532. doi: 10.1128/jvi.55.3.527-532.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Roenhorst H. W., Beelen J. M., Middeldorp J. M., Schirm J., Tegzess A. M., The T. H. Maintenance of cytomegalovirus (CMV) latency and host immune responses of long term renal allograft survivors. II. Secondary CMV infections associated with impaired in vitro proliferative responses to mitogens, allogeneic lymphocytes and CMV infected cells. Clin Exp Immunol. 1985 Jul;61(1):72–79. [PMC free article] [PubMed] [Google Scholar]
  17. Roenhorst H. W., Middeldorp J. M., Beelen J. M., Schirm J., Tegzess A. M., The T. H. Maintenance of cytomegalovirus (CMV) latency and host immune responses of long term renal allograft survivors. I. Prolonged suppression of in vitro lymphocyte responses against CMV infected fibroblasts related to previous secondary CMV infection. Clin Exp Immunol. 1985 Mar;59(3):709–715. [PMC free article] [PubMed] [Google Scholar]
  18. Schirm J., Roenhorst H. W., The T. H. Comparison of in vitro lymphocyte proliferations induced by cytomegalovirus-infected human fibroblasts and cell-free cytomegalovirus. Infect Immun. 1980 Dec;30(3):621–627. doi: 10.1128/iai.30.3.621-627.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schrier R. D., Nelson J. A., Oldstone M. B. Detection of human cytomegalovirus in peripheral blood lymphocytes in a natural infection. Science. 1985 Nov 29;230(4729):1048–1051. doi: 10.1126/science.2997930. [DOI] [PubMed] [Google Scholar]
  20. Schrier R. D., Oldstone M. B. Recent clinical isolates of cytomegalovirus suppress human cytomegalovirus-specific human leukocyte antigen-restricted cytotoxic T-lymphocyte activity. J Virol. 1986 Jul;59(1):127–131. doi: 10.1128/jvi.59.1.127-131.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schrier R. D., Rice G. P., Oldstone M. B. Suppression of natural killer cell activity and T cell proliferation by fresh isolates of human cytomegalovirus. J Infect Dis. 1986 Jun;153(6):1084–1091. doi: 10.1093/infdis/153.6.1084. [DOI] [PubMed] [Google Scholar]
  22. Southern P., Oldstone M. B. Medical consequences of persistent viral infection. N Engl J Med. 1986 Feb 6;314(6):359–367. doi: 10.1056/NEJM198602063140606. [DOI] [PubMed] [Google Scholar]
  23. Stagno S., Whitley R. J. Herpesvirus infections of pregnancy. Part I: Cytomegalovirus and Epstein-Barr virus infections. N Engl J Med. 1985 Nov 14;313(20):1270–1274. doi: 10.1056/NEJM198511143132006. [DOI] [PubMed] [Google Scholar]
  24. Starr S. E., Dalton B., Garrabrant T., Paucker K., Plotkin S. A. Lymphocyte blastogenesis and interferon production in adult human leukocyte cultures stimulated with cytomegalovirus antigens. Infect Immun. 1980 Oct;30(1):17–22. doi: 10.1128/iai.30.1.17-22.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stinski M. F., Mocarski E. S., Thomsen D. R., Urbanowski M. L. Membrane glycoproteins and antigens induced by human cytomegalovirus. J Gen Virol. 1979 Apr;43(1):119–129. doi: 10.1099/0022-1317-43-1-119. [DOI] [PubMed] [Google Scholar]
  26. Stinski M. F. Sequence of protein synthesis in cells infected by human cytomegalovirus: early and late virus-induced polypeptides. J Virol. 1978 Jun;26(3):686–701. doi: 10.1128/jvi.26.3.686-701.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ten Napel C. H., The T. H., Bijker J., De Gast G. C., Langenhuysen M. M. Cytomegalovirus-directed lymphocyte reactivity in healthy adults tested by a CMV-induced lymphocyte transformation test. Clin Exp Immunol. 1977 Jul;29(1):52–60. [PMC free article] [PubMed] [Google Scholar]
  28. Wahren B., Ljungman P., Paulin T., Ringdén O. Enhancive and suppressive effects of cytomegalovirus on human lymphocyte responses in vitro. J Virol. 1986 Jun;58(3):909–913. doi: 10.1128/jvi.58.3.909-913.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Waner J. L., Kong N., Biano S. Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus. Infect Immun. 1983 Sep;41(3):1084–1088. doi: 10.1128/iai.41.3.1084-1088.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wentworth B. B., French L. Plaque assay of cytomegalovirus strains of human origin. Proc Soc Exp Biol Med. 1970 Nov;135(2):253–258. doi: 10.3181/00379727-135-35031. [DOI] [PubMed] [Google Scholar]
  31. ten Napel C. H., The T. H. Acute cytomegalovirus infection and the host immune response. I. Development and maintenance of cytomegalovirus (CMV) induced in vitro lymphocyte reactivity and its relationship to the production of CMV antibodies. Clin Exp Immunol. 1980 Feb;39(2):263–271. [PMC free article] [PubMed] [Google Scholar]

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