Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1995 Dec;69(12):8114–8117. doi: 10.1128/jvi.69.12.8114-8117.1995

Immortalization of human T cells expressing T-cell receptor gamma delta by herpesvirus saimiri.

M Yasukawa 1, Y Inoue 1, N Kimura 1, S Fujita 1
PMCID: PMC189764  PMID: 7494332

Abstract

Herpesvirus saimiri (HVS) has recently been shown to immortalize human CD4+ and CD8+ T cells expressing T-cell receptor alpha beta (TCR-alpha beta) with the maintenance of their original phenotypes and functional properties. However, the immortalization of human T cells expressing TCR-gamma delta by HVS has not been successful. Here we report that HVS can also infect and immortalize human T cells expressing TCR-gamma delta. Two human TCR-gamma delta+ T-cell clones, which continuously proliferated in interleukin-2-containing culture medium without any exogenous stimulation or addition of feeder cells for more than 8 months, were established by HVS infection. Morphologically, the HVS-transformed TCR-gamma delta+ T-cell clones were granular lymphocytes which exhibited wide-range HLA-unrestricted cytotoxicity as untransformed TCR-gamma delta+ T cells. Their phenotypes and cytotoxic activities were not altered during long-term culture. The immortalization of human TCR-gamma delta+ T cells by HVS infection would be useful for functional analysis of this lymphocyte population, which is believed to play an important role in protection against various infectious diseases.

Full Text

The Full Text of this article is available as a PDF (334.1 KB).

Selected References

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

  1. Berend K. R., Jung J. U., Boyle T. J., DiMaio J. M., Mungal S. A., Desrosiers R. C., Lyerly H. K. Phenotypic and functional consequences of herpesvirus saimiri infection of human CD8+ cytotoxic T lymphocytes. J Virol. 1993 Oct;67(10):6317–6321. doi: 10.1128/jvi.67.10.6317-6321.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biesinger B., Müller-Fleckenstein I., Simmer B., Lang G., Wittmann S., Platzer E., Desrosiers R. C., Fleckenstein B. Stable growth transformation of human T lymphocytes by herpesvirus saimiri. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3116–3119. doi: 10.1073/pnas.89.7.3116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Biesinger B., Trimble J. J., Desrosiers R. C., Fleckenstein B. The divergence between two oncogenic Herpesvirus saimiri strains in a genomic region related to the transforming phenotype. Virology. 1990 Jun;176(2):505–514. doi: 10.1016/0042-6822(90)90020-r. [DOI] [PubMed] [Google Scholar]
  4. Bröker B. M., Tsygankov A. Y., Müller-Fleckenstein I., Guse A. H., Chitaev N. A., Biesinger B., Fleckenstein B., Emmrich F. Immortalization of human T cell clones by Herpesvirus saimiri. Signal transduction analysis reveals functional CD3, CD4, and IL-2 receptors. J Immunol. 1993 Aug 1;151(3):1184–1192. [PubMed] [Google Scholar]
  5. De Carli M., Berthold S., Fickenscher H., Fleckenstein I. M., D'Elios M. M., Gao Q., Biagiotti R., Giudizi M. G., Kalden J. R., Fleckenstein B. Immortalization with herpesvirus saimiri modulates the cytokine secretion profile of established Th1 and Th2 human T cell clones. J Immunol. 1993 Nov 1;151(9):5022–5030. [PubMed] [Google Scholar]
  6. Haas W., Pereira P., Tonegawa S. Gamma/delta cells. Annu Rev Immunol. 1993;11:637–685. doi: 10.1146/annurev.iy.11.040193.003225. [DOI] [PubMed] [Google Scholar]
  7. Havran W. L., Boismenu R. Activation and function of gamma delta T cells. Curr Opin Immunol. 1994 Jun;6(3):442–446. doi: 10.1016/0952-7915(94)90125-2. [DOI] [PubMed] [Google Scholar]
  8. Inatsuki A., Yasukawa M., Kobayashi Y. Functional alterations of herpes simplex virus-specific CD4+ multifunctional T cell clones following infection with human T lymphotropic virus type I. J Immunol. 1989 Aug 15;143(4):1327–1333. [PubMed] [Google Scholar]
  9. Inatsuki A., Yasukawa M., Kobayashi Y. The effect of human T cell leukaemia virus type I infection on a herpes simplex virus-specific CD8+ cytotoxic T cell clone. Br J Haematol. 1991 Mar;77(3):311–314. doi: 10.1111/j.1365-2141.1991.tb08576.x. [DOI] [PubMed] [Google Scholar]
  10. Meinl E., Hohlfeld R., Wekerle H., Fleckenstein B. Immortalization of human T cells by Herpesvirus saimiri. Immunol Today. 1995 Feb;16(2):55–58. doi: 10.1016/0167-5699(95)80087-5. [DOI] [PubMed] [Google Scholar]
  11. Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mittrücker H. W., Müller-Fleckenstein I., Fleckenstein B., Fleischer B. Herpes virus saimiri-transformed human T lymphocytes: normal functional phenotype and preserved T cell receptor signalling. Int Immunol. 1993 Aug;5(8):985–990. doi: 10.1093/intimm/5.8.985. [DOI] [PubMed] [Google Scholar]
  13. Miyoshi I., Kubonishi I., Yoshimoto S., Akagi T., Ohtsuki Y., Shiraishi Y., Nagata K., Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
  14. Okada M., Yoshimura N., Kaieda T., Yamamura Y., Kishimoto T. Establishment and characterization of human T hybrid cells secreting immunoregulatory molecules. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7717–7721. doi: 10.1073/pnas.78.12.7717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Popovic M., Flomenberg N., Volkman D. J., Mann D., Fauci A. S., Dupont B., Gallo R. C. Alteration of T-cell functions by infection with HTLV-I or HTLV-II. Science. 1984 Oct 26;226(4673):459–462. doi: 10.1126/science.6093248. [DOI] [PubMed] [Google Scholar]
  16. Saito H., Kranz D. M., Takagaki Y., Hayday A. C., Eisen H. N., Tonegawa S. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. 1984 Jun 28-Jul 4Nature. 309(5971):757–762. doi: 10.1038/309757a0. [DOI] [PubMed] [Google Scholar]
  17. Simmer B., Alt M., Buckreus I., Berthold S., Fleckenstein B., Platzer E., Grassmann R. Persistence of selectable herpesvirus saimiri in various human haematopoietic and epithelial cell lines. J Gen Virol. 1991 Aug;72(Pt 8):1953–1958. doi: 10.1099/0022-1317-72-8-1953. [DOI] [PubMed] [Google Scholar]
  18. Weber F., Meinl E., Drexler K., Czlonkowska A., Huber S., Fickenscher H., Müller-Fleckenstein I., Fleckenstein B., Wekerle H., Hohlfeld R. Transformation of human T-cell clones by Herpesvirus saimiri: intact antigen recognition by autonomously growing myelin basic protein-specific T cells. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11049–11053. doi: 10.1073/pnas.90.23.11049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yasukawa M., Inatsuki A., Horiuchi T., Kobayashi Y. Functional heterogeneity among herpes simplex virus-specific human CD4+ T cells. J Immunol. 1991 Feb 15;146(4):1341–1347. [PubMed] [Google Scholar]
  20. Yasukawa M., Inatsuki A., Yakushijin Y., Kobayashi Y. Human T-cell leukemia virus type I(HTLV-I) infection of T cells bearing T-cell receptor gamma delta: effects of HTLV-I infection on cytotoxicity. Int J Cancer. 1992 Feb 1;50(3):431–437. doi: 10.1002/ijc.2910500318. [DOI] [PubMed] [Google Scholar]
  21. Yasukawa M., Zarling J. M. Autologous herpes simplex virus-infected cells are lysed by human natural killer cells. J Immunol. 1983 Oct;131(4):2011–2016. [PubMed] [Google Scholar]
  22. Yasukawa M., Zarling J. M. Human cytotoxic T cell clones directed against herpes simplex virus-infected cells. I. Lysis restricted by HLA class II MB and DR antigens. J Immunol. 1984 Jul;133(1):422–427. [PubMed] [Google Scholar]
  23. Yssel H., de Waal Malefyt R., Duc Dodon M. D., Blanchard D., Gazzolo L., de Vries J. E., Spits H. Human T cell leukemia/lymphoma virus type I infection of a CD4+ proliferative/cytotoxic T cell clone progresses in at least two distinct phases based on changes in function and phenotype of the infected cells. J Immunol. 1989 Apr 1;142(7):2279–2289. [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES