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. 1987 Dec;62(4):647–654.

In vitro expansion of Epstein-Barr virus-specific HLA-restricted cytotoxic T cells direct from the blood of infectious mononucleosis patients.

G Strang 1, A B Rickinson 1
PMCID: PMC1454146  PMID: 2828228

Abstract

The cytotoxic T-cell response induced by primary Epstein-Barr virus (EBV) infection and detectable in the blood of infectious mononucleosis (IM) patients shows several unusual features when tested in in vitro assays. Lysis of EBV-transformed target lines occurs with no apparent HLA restriction, and the putative EBV specificity of the response has been seriously questioned. In the present work we show that the primary T-cell response in IM is polyclonal and indeed does contain a virus-specific HLA class I antigen-restricted component, which can be selectively expanded in vitro in the presence of appropriate stimulator cells and IL-2. This allows functional analysis of the virus-specific component of the response in the absence of co-resident reactivities. Studies on blood samples taken from individuals in the acute phase of IM and again post-convalescence suggest that functionally similar populations of HLA class I-restricted cytotoxic T cells are involved in the control of both the primary and persistent phase of EBV infection.

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Selected References

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

  1. Bakacs T., Svedmyr E., Klein E. EBV-related cytotoxicity of Fc receptor negative T lymphocytes separated from the blood of infectious mononucleosis patients. Cancer Lett. 1978 Apr;4(4):185–189. doi: 10.1016/s0304-3835(78)94347-1. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Crawford D. H., Brickell P., Tidman N., McConnell I., Hoffbrand A. V., Janossy G. Increased numbers of cells with suppressor T cell phenotype in the peripheral blood of patients with infectious mononucleosis. Clin Exp Immunol. 1981 Feb;43(2):291–297. [PMC free article] [PubMed] [Google Scholar]
  4. Dongworth D. W., Gotch F. M., Hildreth J. E., Morris A., McMichael A. J. Effects of monoclonal antibodies to the alpha and beta chains of the human lymphocyte function-associated (H-LFA-1) antigen on T lymphocyte functions. Eur J Immunol. 1985 Sep;15(9):888–892. doi: 10.1002/eji.1830150905. [DOI] [PubMed] [Google Scholar]
  5. Gaston J. S., Rickinson A. B., Epstein M. A. Cross-reactivity of self-HLA-restricted Epstein-Barr virus-specific cytotoxic T lymphocytes for allo-HLA determinants. J Exp Med. 1983 Dec 1;158(6):1804–1821. doi: 10.1084/jem.158.6.1804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gaston J. S., Rickinson A. B., Epstein M. A. Epstein-Barr virus-specific cytotoxic T lymphocytes as probes of HLA polymorphism. Heterogeneity of T cell-restricting determinants associated with the serologically defined HLA-A2 antigen. J Exp Med. 1983 Aug 1;158(2):280–293. doi: 10.1084/jem.158.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Klein E., Ernberg I., Masucci M. G., Szigeti R., Wu Y. T., Masucci G., Svedmyr E. T-cell response to B-cells and Epstein-Barr virus antigens in infectious mononucleosis. Cancer Res. 1981 Nov;41(11 Pt 1):4210–4215. [PubMed] [Google Scholar]
  8. Miller G., Shope T., Lisco H., Stitt D., Lipman M. Epstein-Barr virus: transformation, cytopathic changes, and viral antigens in squirrel monkey and marmoset leukocytes. Proc Natl Acad Sci U S A. 1972 Feb;69(2):383–387. doi: 10.1073/pnas.69.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Moss D. J., Bishop C. J., Burrows S. R., Ryan J. M. T lymphocytes in infectious mononucleosis. I. T cell death in vitro. Clin Exp Immunol. 1985 Apr;60(1):61–69. [PMC free article] [PubMed] [Google Scholar]
  10. Moss D. J., Wallace L. E., Rickinson A. B., Epstein M. A. Cytotoxic T cell recognition of Epstein-Barr virus-infected B cells. I. Specificity and HLA restriction of effector cells reactivated in vitro. Eur J Immunol. 1981 Sep;11(9):686–693. doi: 10.1002/eji.1830110904. [DOI] [PubMed] [Google Scholar]
  11. Patel P. C., Dorval G., Menezes J. Cytotoxic effector cells from infectious mononucleosis patients in the acute phase do not specifically kill Epstein-Barr virus genome-carrying lymphoid cell lines. Infect Immun. 1982 Oct;38(1):251–259. doi: 10.1128/iai.38.1.251-259.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rabin H., Hopkins R. F., 3rd, Ruscetti F. W., Neubauer R. H., Brown R. L., Kawakami T. G. Spontaneous release of a factor with properties of T cell growth factor from a continuous line of primate tumor T cells. J Immunol. 1981 Nov;127(5):1852–1856. [PubMed] [Google Scholar]
  13. Reinherz E. L., O'Brien C., Rosenthal P., Schlossman S. F. The cellular basis for viral-induced immunodeficiency: analysis by monoclonal antibodies. J Immunol. 1980 Sep;125(3):1269–1274. [PubMed] [Google Scholar]
  14. Robinson J., Smith D., Niederman J. Mitotic EBNA-positive lymphocytes in peripheral blood during infectious mononucleosis. Nature. 1980 Sep 25;287(5780):334–335. doi: 10.1038/287334a0. [DOI] [PubMed] [Google Scholar]
  15. Royston I., Sullivan J. L., Periman P. O., Perlin E. Cell-mediated immunity to Epstein-Barr-virus-transformed lymphoblastoid cells in acute infectious mononucleosis. N Engl J Med. 1975 Dec 4;293(23):1159–1163. doi: 10.1056/NEJM197512042932301. [DOI] [PubMed] [Google Scholar]
  16. Seeley J. K., Golub S. H. Studies on cytotoxicity generated in human mixed lymphocyte cultures. I. Time course and target spectrum of several distinct concomitant cytotoxic activities. J Immunol. 1978 Apr;120(4):1415–1422. [PubMed] [Google Scholar]
  17. 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]
  18. Strang G., Rickinson A. B. Multiple HLA class I-dependent cytotoxicities constitute the "non-HLA-restricted" response in infectious mononucleosis. Eur J Immunol. 1987 Jul;17(7):1007–1013. doi: 10.1002/eji.1830170717. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Swain S. L. T cell subsets and the recognition of MHC class. Immunol Rev. 1983;74:129–142. doi: 10.1111/j.1600-065x.1983.tb01087.x. [DOI] [PubMed] [Google Scholar]
  21. Walker L., Guy G., Brown G., Rowe M., Milner A. E., Gordon J. Control of human B-lymphocyte replication. I. Characterization of novel activation states that precede the entry of G0 B cells into cycle. Immunology. 1986 Aug;58(4):583–589. [PMC free article] [PubMed] [Google Scholar]
  22. Wallace L. E., Moss D. J., Rickinson A. B., McMichael A. J., Epstein M. A. Cytotoxic T cell recognition of Epstein-Barr virus-infected B cells. II. Blocking studies with monoclonal antibodies to HLA determinants. Eur J Immunol. 1981 Sep;11(9):694–699. doi: 10.1002/eji.1830110905. [DOI] [PubMed] [Google Scholar]
  23. Wallace L. E., Rickinson A. B., Rowe M., Moss D. J., Allen D. J., Epstein M. A. Stimulation of human lymphocytes with irradiated cells of the autologous Epstein-Barr virus-transformed cell line. I. Virus-specific and nonspecific components of the cytotoxic response. Cell Immunol. 1982 Feb;67(1):129–140. doi: 10.1016/0008-8749(82)90205-2. [DOI] [PubMed] [Google Scholar]
  24. Wallace L. E., Rowe M., Gaston J. S., Rickinson A. B., Epstein M. A. Cytotoxic T cell recognition of Epstein-Barr virus-infected B cells. III. Establishment of HLA-restricted cytotoxic T cell lines using interleukin 2. Eur J Immunol. 1982 Dec;12(12):1012–1018. doi: 10.1002/eji.1830121206. [DOI] [PubMed] [Google Scholar]
  25. von Boehmer H., Hengartner H., Nabholz M., Lernhardt W., Schreier M. H., Haas W. Fine specificity of a continuously growing killer cell clone specific for H-Y antigen. Eur J Immunol. 1979 Aug;9(8):592–597. doi: 10.1002/eji.1830090804. [DOI] [PubMed] [Google Scholar]

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