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. 1987 May;68(2):251–258.

Defective generation of killer cells against spontaneously Epstein-Barr virus (EBV)-transformed autologous B cells in a fatal EBV infection.

M Yanagisawa 1, M Kato 1, K Ikeno 1, T Kobayashi 1, Y Miyagawa 1, A Komiyama 1, T Akabane 1
PMCID: PMC1542730  PMID: 2820633

Abstract

Killer cell activities were analysed in a 16-month-old boy with a sporadic form of fatal Epstein-Barr virus (EBV) infection, and compared with those in three patients with acute infectious mononucleosis (IM). We used spontaneously EBV-transformed autologous lymphoblastoid B cell lines (LCL) as target cells, because the results obtained with such targets can be expected to reflect most accurately the killer-versus-target reaction in vivo. The patient's fresh peripheral blood mononuclear cells (PBMC) had relatively high natural killer (NK) cell activity against K562 cells (128% of the control value), but they did not kill his autologous LCL. The patient's PBMC, unlike PBMC of acute IM, showed no cytotoxicity against Raji cells and autologous LCL after 5 days' culture in the presence of recombinant interleukin 2 (rIL-2), indicating defective generation of lymphokine-activated killer (LAK) cells. The patient's PBMC, unlike PBMC of acute IM, also could not induce cytotoxicity against autologous LCL when cocultured with mitomycin C-treated respective autologous LCL for 7 days. The addition of rIL-2 to the culture significantly restored their ability to generate cytotoxic T lymphocytes (CTL) against his LCL: the percent cytotoxicity value rose from 3.0% to 37.7%. With respect to this, the endogenous IL-2 production by the patient's PBMC was deficient. These results suggest that the defective EBV-selective CTL generation was due to deficient IL-2 production. The failure of the killer cells to eliminate EBV-infected cells seems to have been responsible for the patient's unusual course after primary EBV infection.

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Selected References

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  1. Ando I., Morgan G., Levinsky R. J., Crawford D. H. A family study of the X-linked lymphoproliferative syndrome: evidence for a B cell defect contributing to the immunodeficiency. Clin Exp Immunol. 1986 Feb;63(2):271–279. [PMC free article] [PubMed] [Google Scholar]
  2. Bar R. S., DeLor C. J., Clausen K. P., Hurtubise P., Henle W., Hewetson J. F. Fatal infectious mononucleosis in a family. N Engl J Med. 1974 Feb 14;290(7):363–367. doi: 10.1056/NEJM197402142900704. [DOI] [PubMed] [Google Scholar]
  3. Bishop C. J., Moss D. J., Ryan J. M., Burrows S. R. T lymphocytes in infectious mononucleosis. II. Response in vitro to interleukin-2 and establishment of T cell lines. Clin Exp Immunol. 1985 Apr;60(1):70–77. [PMC free article] [PubMed] [Google Scholar]
  4. Blazar B., Patarroyo M., Klein E., Klein G. Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate. J Exp Med. 1980 Mar 1;151(3):614–627. doi: 10.1084/jem.151.3.614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chouaib S., Fradelizi D. The mechanism of inhibition of human IL 2 production. J Immunol. 1982 Dec;129(6):2463–2468. [PubMed] [Google Scholar]
  6. Grimm E. A., Ramsey K. M., Mazumder A., Wilson D. J., Djeu J. Y., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med. 1983 Mar 1;157(3):884–897. doi: 10.1084/jem.157.3.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Harada S., Sakamoto K., Seeley J. K., Lindsten T., Bechtold T., Yetz J., Rogers G., Pearson G., Purtilo D. T. Immune deficiency in the X-linked lymphoproliferative syndrome. I. Epstein-Barr virus-specific defects. J Immunol. 1982 Dec;129(6):2532–2535. [PubMed] [Google Scholar]
  8. Hooton J. W., Gibbs C., Paetkau V. Interaction of interleukin 2 with cells: quantitative analysis of effects. J Immunol. 1985 Oct;135(4):2464–2473. [PubMed] [Google Scholar]
  9. Kibler R., Lucas D. O., Hicks M. J., Poulos B. T., Jones J. F. Immune function in chronic active Epstein-Barr virus infection. J Clin Immunol. 1985 Jan;5(1):46–54. doi: 10.1007/BF00915168. [DOI] [PubMed] [Google Scholar]
  10. Komiyama A., Kawai H., Miyagawa Y., Akabane T. Childhood lymphoblastic leukemia with natural killer activity: establishment of the leukemia cell lines retaining the activity. Blood. 1982 Dec;60(6):1429–1436. [PubMed] [Google Scholar]
  11. Martin P. J., Shulman H. M., Schubach W. H., Hansen J. A., Fefer A., Miller G., Thomas E. D. Fatal Epstein-Barr-virus-associated proliferation of donor B cells after treatment of acute graft-versus-host disease with a murine anti-T-cell antibody. Ann Intern Med. 1984 Sep;101(3):310–315. doi: 10.7326/0003-4819-101-3-310. [DOI] [PubMed] [Google Scholar]
  12. Minato N., Bloom B. R., Jones C., Holland J., Reid L. M. Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice. J Exp Med. 1979 May 1;149(5):1117–1133. doi: 10.1084/jem.149.5.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Phillips J. H., Le A. M., Lanier L. L. Natural killer cells activated in a human mixed lymphocyte response culture identified by expression of Leu-11 and class II histocompatibility antigens. J Exp Med. 1984 Apr 1;159(4):993–1008. doi: 10.1084/jem.159.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Purtilo D. T., Cassel C. K., Yang J. P., Harper R. X-linked recessive progressive combined variable immunodeficiency (Duncan's disease). Lancet. 1975 Apr 26;1(7913):935–940. doi: 10.1016/s0140-6736(75)92004-8. [DOI] [PubMed] [Google Scholar]
  15. Risdall R. J., McKenna R. W., Nesbit M. E., Krivit W., Balfour H. H., Jr, Simmons R. L., Brunning R. D. Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer. 1979 Sep;44(3):993–1002. doi: 10.1002/1097-0142(197909)44:3<993::aid-cncr2820440329>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  16. Rooney C. M., Rickinson A. B., Moss D. J., Lenoir G. M., Epstein M. A. Paired Epstein-Barr virus-carrying lymphoma and lymphoblastoid cell lines from Burkitt's lymphoma patients: comparative sensitivity to non-specific and to allo-specific cytotoxic responses in vitro. Int J Cancer. 1984 Sep 15;34(3):339–348. doi: 10.1002/ijc.2910340310. [DOI] [PubMed] [Google Scholar]
  17. Rosenberg S. A., Lotze M. T., Muul L. M., Leitman S., Chang A. E., Ettinghausen S. E., Matory Y. L., Skibber J. M., Shiloni E., Vetto J. T. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985 Dec 5;313(23):1485–1492. doi: 10.1056/NEJM198512053132327. [DOI] [PubMed] [Google Scholar]
  18. Rousset F., Souillet G., Roncarolo M. G., Lamelin J. P. Studies of EBV-lymphoid cell interactions in two patients with the X-linked lymphoproliferative syndrome: normal EBV-specific HLA-restricted cytotoxicity. Clin Exp Immunol. 1986 Feb;63(2):280–289. [PMC free article] [PubMed] [Google Scholar]
  19. Seeley J., Svedmyr E., Weiland O., Klein G., Moller E., Eriksson E., Andersson K., van der Waal L. Epstein Barr virus selective T cells in infectious mononucleosis are not restricted to HLA-A and B antigens. J Immunol. 1981 Jul;127(1):293–300. [PubMed] [Google Scholar]
  20. Slovin S. F., Schooley R. T., Thorley-Lawson D. A. Analysis of cellular immune response to EBV by using cloned T cell lines. J Immunol. 1983 May;130(5):2127–2132. [PubMed] [Google Scholar]
  21. Sullivan J. L., Byron K. S., Brewster F. E., Baker S. M., Ochs H. D. X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency. J Clin Invest. 1983 Jun;71(6):1765–1778. doi: 10.1172/JCI110932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sullivan J. L., Woda B. A., Herrod H. G., Koh G., Rivara F. P., Mulder C. Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies. Blood. 1985 May;65(5):1097–1104. [PubMed] [Google Scholar]
  23. Ting C. C., Hargrove M. E., Loh N. N. Production of T cell differentiation factor in syngeneic lymphocyte macrophage culture for cytotoxic T lymphocyte generation. J Immunol. 1986 Mar 1;136(5):1726–1733. [PubMed] [Google Scholar]
  24. Tosato G., Blaese R. M. Epstein-Barr virus infection and immunoregulation in man. Adv Immunol. 1985;37:99–149. doi: 10.1016/s0065-2776(08)60339-9. [DOI] [PubMed] [Google Scholar]
  25. Wee S. L., Ochoa A. C., Bach F. H. Human alloreactive CTL clones: loss and reacquisition of specific cytolytic activity can be regulated by "recombinant" interleukin 2. J Immunol. 1985 Jan;134(1):310–313. [PubMed] [Google Scholar]
  26. Wilson E. R., Malluh A., Stagno S., Crist W. M. Fatal Epstein-Barr virus-associated hemophagocytic syndrome. J Pediatr. 1981 Feb;98(2):260–262. doi: 10.1016/s0022-3476(81)80654-3. [DOI] [PubMed] [Google Scholar]
  27. Yang H., Welsh R. M. Induction of alloreactive cytotoxic T cells by acute virus infection of mice. J Immunol. 1986 Feb 15;136(4):1186–1193. [PubMed] [Google Scholar]
  28. Zarling J. M., Dierckins M. S., Sevenich E. A., Clouse K. A. Stimulation with autologous lymphoblastoid cell lines: lysis of Epstein-Barr virus-positive and -negative cell lines by two phenotypically distinguishable effector cell populations. J Immunol. 1981 Nov;127(5):2118–2123. [PubMed] [Google Scholar]

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