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. 1980 Sep;29(3):945–952. doi: 10.1128/iai.29.3.945-952.1980

Relationship of in vitro immune responses to Epstein-Barr herpesvirus and severity of infectious mononucleosis.

K Goldstein, P K Lai, M Lightfoote, A P Andrese, D Fuccillo, R J Connor, P H Levine
PMCID: PMC551222  PMID: 6253402

Abstract

Immune responses to Epstein-Barr herpesvirus (EBV) and EBV-related antigens were studied serially in 18 patients with heterophil antibody-positive infectious mononucleosis and in 18 control subjects. Enhanced cellular immune responses to EBV particles and to EBV intracellular soluble antigens were found in the patients at convalescence, suggesting that the development of specific cellular immune responses was associated with apparent control of the virus infection. In addition, a correlation between severity of disease and specific cellular immune response was found. Patients with severe clinical signs were found to have a more active cellular immune response to EBV intracellular soluble antigens early in the infection compared with patients with mild disease. This suggests that an increased immune reactivity to intracellular antigens during the early part of the illness is related to the severity of clinical manifestations in infectious mononucleosis. Serum antibody to viral capsid antigen and early antigen was not related to the severity of clinical disease.

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Selected References

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

  1. BACH F., HIRSCHHORN K. LYMPHOCYTE INTERACTION: A POTENTIAL HISTOCOMPATIBILITY TEST IN VITRO. Science. 1964 Feb 21;143(3608):813–814. doi: 10.1126/science.143.3608.813. [DOI] [PubMed] [Google Scholar]
  2. Bendixen G., Soborg M. A leucocyte migration technique for in vitro detection of cellular (delayed type) hypersensitivity in man. Dan Med Bull. 1969 Jan;16(1):1–6. [PubMed] [Google Scholar]
  3. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. 3. Regression infectious foci. J Exp Med. 1971 May 1;133(5):1090–1104. doi: 10.1084/jem.133.5.1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. I. The effects of anti-thymocyte serum. J Exp Med. 1970 Nov;132(5):1035–1054. doi: 10.1084/jem.132.5.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blanden R. V. Mechanisms of recovery from a generalized viral infection: mousepox. II. Passive transfer of recovery mechanisms with immune lymphoid cells. J Exp Med. 1971 May 1;133(5):1074–1089. doi: 10.1084/jem.133.5.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bloom B. R. In vitro approaches to the mechanism of cell-mediated immune reactions. Adv Immunol. 1971;13:101–208. doi: 10.1016/s0065-2776(08)60184-4. [DOI] [PubMed] [Google Scholar]
  7. Carter R. L. Infectious mononucleosis: model for self-limiting lymphoproliferation. Lancet. 1975 Apr 12;1(7911):846–849. doi: 10.1016/s0140-6736(75)93014-7. [DOI] [PubMed] [Google Scholar]
  8. Chan S. H., Wallen W. C., Levine P. H., Periman P., Perlin E. Lymphocyte responses to EBV-associated antigens in infectious mononucleosis, and Hodgkin's and non-Hodgkin's lymphoma patients, with the leukocyte adherence inhibition assay. Int J Cancer. 1977 Mar 15;19(3):356–363. doi: 10.1002/ijc.2910190312. [DOI] [PubMed] [Google Scholar]
  9. DAVID J. R., AL-ASKARI S., LAWRENCE H. S., THOMAS L. DELAYED HYPERSENSITIVITY IN VITRO. I. THE SPECIFICITY OF INHIBITION OF CELL MIGRATION BY ANTIGENS. J Immunol. 1964 Aug;93:264–273. [PubMed] [Google Scholar]
  10. Epstein M. A., Achong B. G. The EB virus. Annu Rev Microbiol. 1973;27:413–436. doi: 10.1146/annurev.mi.27.100173.002213. [DOI] [PubMed] [Google Scholar]
  11. Evans A. S., Niederman J. C., McCollum R. W. Seroepidemiologic studies of infectious mononucleosis with EB virus. N Engl J Med. 1968 Nov 21;279(21):1121–1127. doi: 10.1056/NEJM196811212792101. [DOI] [PubMed] [Google Scholar]
  12. GELB D., WEST M., ZIMMERMAN H. J. Serum enzymes in disease. IX. Analysis of factors responsible for elevated values in infectious mononucleosis. Am J Med. 1962 Aug;33:249–261. doi: 10.1016/0002-9343(62)90023-2. [DOI] [PubMed] [Google Scholar]
  13. GEORGE M., VAUGHAN J. H. In vitro cell migration as a model for delayed hypersensitivity. Proc Soc Exp Biol Med. 1962 Nov;111:514–521. doi: 10.3181/00379727-111-27841. [DOI] [PubMed] [Google Scholar]
  14. Gerber P., Lucas S. J. In vitro stimulation of human lymphocytes by Epstein-Barr virus. Cell Immunol. 1972 Oct;5(2):318–324. doi: 10.1016/0008-8749(72)90057-3. [DOI] [PubMed] [Google Scholar]
  15. Golubjatnikov R., Allen V. D., Steadman M., Del Pilar Olmos Blanc, Inhorn S. L. Prevalence of antibodies to Epstein-Barr virus, cytomegalovirus and Toxoplasma in a Mexican highland community. Am J Epidemiol. 1973 Feb;97(2):116–124. doi: 10.1093/oxfordjournals.aje.a121488. [DOI] [PubMed] [Google Scholar]
  16. Granlund D. J., Andrese A. P. Detection of Epstein-Barr virus antigens with enzyme-conjugated antibody. Int J Cancer. 1977 Oct 15;20(4):495–499. doi: 10.1002/ijc.2910200404. [DOI] [PubMed] [Google Scholar]
  17. Haider S., Coutinho M. de L., Emond R. T., Sutton R. N. Tuberculin anergy and infectious mononucleosis. Lancet. 1973 Jul 14;2(7820):74–74. doi: 10.1016/s0140-6736(73)93265-0. [DOI] [PubMed] [Google Scholar]
  18. Hellström I. A colony inhibition (CI) technique for demonstration of tumor cell destruction by lymphoid cells in vitro. Int J Cancer. 1967 Jan 15;2(1):65–68. doi: 10.1002/ijc.2910020111. [DOI] [PubMed] [Google Scholar]
  19. Henle G., Henle W., Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A. 1968 Jan;59(1):94–101. doi: 10.1073/pnas.59.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Henle G., Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. doi: 10.1128/jb.91.3.1248-1256.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Henle W., Henle G. E., Horwitz C. A. Epstein-Barr virus specific diagnostic tests in infectious mononucleosis. Hum Pathol. 1974 Sep;5(5):551–565. doi: 10.1016/s0046-8177(74)80006-7. [DOI] [PubMed] [Google Scholar]
  22. Henle W., Henle G., Niederman J. C., Klemola E., Haltia K. Antibodies to early antigens induced by Epstein-Barr virus in infectious mononucleosis. J Infect Dis. 1971 Jul;124(1):58–67. doi: 10.1093/infdis/124.1.58. [DOI] [PubMed] [Google Scholar]
  23. Hirsch M. S., Murphy F. A. Effects of anti-lymphoid sera on viral infections. Lancet. 1968 Jul 6;2(7558):37–40. doi: 10.1016/s0140-6736(68)92904-8. [DOI] [PubMed] [Google Scholar]
  24. Joncas J. H. Clinical significance of the EB herpesvirus infection in man. Prog Med Virol. 1972;14:200–240. [PubMed] [Google Scholar]
  25. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  26. Lai P. K., Alpers M. P., MacKay-Scollay E. M. Development of cell-mediated immunity to Epstein-Barr herpesvirus in infectious mononucleosis as shown by leukocyte migration inhibition. Infect Immun. 1977 Jul;17(1):28–35. doi: 10.1128/iai.17.1.28-35.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lai P. K., Alpers M. P., MacKay-Scollay E. M. Epstein-Barr herpesvirus infection: inhibition by immunologically induced mediators with interferon-like properties. Int J Cancer. 1977 Jul 15;20(1):21–29. doi: 10.1002/ijc.2910200106. [DOI] [PubMed] [Google Scholar]
  28. Lai P. K. Infectious mononucleosis: recognition and management. Hosp Pract. 1977 Aug;12(8):47–52. doi: 10.1080/21548331.1977.11707175. [DOI] [PubMed] [Google Scholar]
  29. Lai P. K., Mackay-Scollay E. M., Alpers M. P. Epidemiological studies of Epstein-Barr herpesvirus infection in Western Australia. J Hyg (Lond) 1975 Jun;74(3):329–337. doi: 10.1017/s0022172400046842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lai P. K., Mackay-Scollay E. M., Fimmel P. J., Alpers M. P., Keast D. Cell-mediated immunity to Epstein-Barr virus and a blocking factor in patients with infectious mononucleosis. Nature. 1974 Dec 13;252(5484):608–610. doi: 10.1038/252608a0. [DOI] [PubMed] [Google Scholar]
  31. Mangi R. J., Niederman J. C., Kelleher J. E., Jr, Dwyer J. M., Evans A. S., Kantor F. S. Depression of cell-mediated immunity during acute infectious mononucleosis. N Engl J Med. 1974 Nov 28;291(22):1149–1153. doi: 10.1056/NEJM197411282912202. [DOI] [PubMed] [Google Scholar]
  32. Miller G., Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci U S A. 1973 Jan;70(1):190–194. doi: 10.1073/pnas.70.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nahmias A. J., Dowdle W. R., Josey W. E., Naib Z. M., Painter L. M., Luce C. Newborn infection with Herpesvirus hominis types 1 and 2. J Pediatr. 1969 Dec;75(6):1194–1203. doi: 10.1016/s0022-3476(69)80375-6. [DOI] [PubMed] [Google Scholar]
  34. Nahmias A. J., Griffith D., Salsbury C., Yoshida K. Thymic aplasia with lymphopenia, plasma cells, and normal immunoglobulins. Relation to measles virus infection. JAMA. 1967 Sep 4;201(10):729–734. [PubMed] [Google Scholar]
  35. Niederman J. C., Evans A. S., Subrahmanyan L., McCollum R. W. Prevalence, incidence and persistence of EB virus antibody in young adults. N Engl J Med. 1970 Feb 12;282(7):361–365. doi: 10.1056/NEJM197002122820704. [DOI] [PubMed] [Google Scholar]
  36. Nikoskelainen J., Ablashi D. V., Isenberg R. A., Neel E. U., Miller R. G., Stevens D. A. Cellular immunity in infectious mononucleosis. II. Specific reactivity to Epstein-Barr Virus antigens and correlation with clinical and hematologic parameters. J Immunol. 1978 Oct;121(4):1239–1244. [PubMed] [Google Scholar]
  37. PULVERTAFT J. V. A STUDY OF MALIGNANT TUMOURS IN NIGERIA BY SHORT-TERM TISSUE CULTURE. J Clin Pathol. 1965 May;18:261–273. doi: 10.1136/jcp.18.3.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pereira M. S., Blake J. M., Macrae A. D. EB virus antibody at different ages. Br Med J. 1969 Nov 29;4(5682):526–527. doi: 10.1136/bmj.4.5682.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Periman P., Levine P. H., Ablashi D. V., Royston I. Cell mediated immunity during infectious mononucleosis to Epstein-Barr virus associated antigens. Int J Cancer. 1977 Oct 15;20(4):506–511. doi: 10.1002/ijc.2910200406. [DOI] [PubMed] [Google Scholar]
  40. Svedmyr E., Jondal M. Cytotoxic effector cells specific for B Cell lines transformed by Epstein-Barr virus are present in patients with infectious mononucleosis. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1622–1626. doi: 10.1073/pnas.72.4.1622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Takasugi M., Klein E. A microassay for cell-mediated immunity. Transplantation. 1970 Mar;9(3):219–227. doi: 10.1097/00007890-197003000-00005. [DOI] [PubMed] [Google Scholar]
  42. Twomey J. J. Abnormalities in the mixed leukocyte reaction during infectious mononucleosis. J Immunol. 1974 Jun;112(6):2278–2281. [PubMed] [Google Scholar]
  43. Wilton J. M., Ivanyi L., Lehner T. Cell-mediated immunity in Herpesvirus hominis infections. Br Med J. 1972 Mar 18;1(5802):723–726. doi: 10.1136/bmj.1.5802.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Ziegler J. L., Magrath I. T., Gerber P., Levine P. H. Epstein-Barr virus and human malignancy. Ann Intern Med. 1977 Mar;86(3):323–336. doi: 10.7326/0003-4819-86-3-323. [DOI] [PubMed] [Google Scholar]

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