Abstract
Herpes virus saimiri (HVS) immortalizes T lymphocytes from a variety of primates and causes acute T cell lymphomas and leukemias in nonnatural primate hosts. Here we have analyzed the requirements for growth of three HVS-transformed human T cell lines. The cells expressed the phenotype of activated T cells: two were CD4+, and one was CD8+. All three cells responded to all allogeneic human cell lines tested with enhanced proliferation, production of interleukin 2 (IL-2), and increased expression of the IL-2 receptor. Binding of CD2 to its ligand CD58 was the critical event mediating stimulation because: (a) monoclonal antibodies (mAbs) to CD2 and to CD58, but not to a variety of other surface structures, blocked induced and spontaneous proliferation and IL-2 production; (b) only anti-CD2 mAbs were stimulatory if crosslinked; (c) a nonstimulatory cell was rendered stimulatory by CD58 transfection; and (d) the cells responded specifically to CD58 on sheep red blood cells. Growth of the cells required activation because cyclosporin A and FK506 blocked stimulator cell-induced IL-2 production and proliferation as well as the spontaneous growth of the lines. Antibodies to the IL-2 receptor reduced proliferation of the cells and blocked IL-2 utilization. Taken together, these results show that HVS-transformed T cells proliferate in response to CD2-mediated contact with stimulator cells or with each other in an IL-2-dependent fashion. They suggest that HVS transforms human T cells to an activation-dependent autocrine growth.
Full Text
The Full Text of this article is available as a PDF (528.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Brottier P., Boumsell L., Gelin C., Bernard A. T cell activation via CD2 [T, gp50] molecules: accessory cells are required to trigger T cell activation via CD2-D66 plus CD2-9.6/T11(1) epitopes. J Immunol. 1985 Sep;135(3):1624–1631. [PubMed] [Google Scholar]
- Dautry-Varsat A., Hémar A., Cornet V., Duprez V. Autocrine growth of a human T-cell line is inhibited by cyclosporin A. Blood. 1988 Aug;72(2):588–592. [PubMed] [Google Scholar]
- Depper J. M., Leonard W. J., Robb R. J., Waldmann T. A., Greene W. C. Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation. J Immunol. 1983 Aug;131(2):690–696. [PubMed] [Google Scholar]
- Duprez V., Lenoir G., Dautry-Varsat A. Autocrine growth stimulation of a human T-cell lymphoma line by interleukin 2. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6932–6936. doi: 10.1073/pnas.82.20.6932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleischer B. A novel pathway of human T cell activation via a 103 kD T cell activation antigen. J Immunol. 1987 Mar 1;138(5):1346–1350. [PubMed] [Google Scholar]
- Hünig T., Tiefenthaler G., Meyer zum Büschenfelde K. H., Meuer S. C. Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature. 1987 Mar 19;326(6110):298–301. doi: 10.1038/326298a0. [DOI] [PubMed] [Google Scholar]
- Lang R. A., Burgess A. W. Autocrine growth factors and tumourigenic transformation. Immunol Today. 1990 Jul;11(7):244–249. doi: 10.1016/0167-5699(90)90098-t. [DOI] [PubMed] [Google Scholar]
- Moingeon P., Chang H. C., Wallner B. P., Stebbins C., Frey A. Z., Reinherz E. L. CD2-mediated adhesion facilitates T lymphocyte antigen recognition function. Nature. 1989 May 25;339(6222):312–314. doi: 10.1038/339312a0. [DOI] [PubMed] [Google Scholar]
- Schirm S., Müller I., Desrosiers R. C., Fleckenstein B. Herpesvirus saimiri DNA in a lymphoid cell line established by in vitro transformation. J Virol. 1984 Mar;49(3):938–946. doi: 10.1128/jvi.49.3.938-946.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yefenof E., Abboud G., Epszteyn S., Vitetta E. S. Treatment of premalignancy: prevention of lymphoma in radiation leukemia virus-inoculated mice by cyclosporin A and immunotoxin. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):728–732. doi: 10.1073/pnas.89.2.728. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yokochi T., Holly R. D., Clark E. A. B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas. J Immunol. 1982 Feb;128(2):823–827. [PubMed] [Google Scholar]