Abstract
Expression of the pluripotent molecule TNF in a focused and antigen- restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen- specific fashion.
Full Text
The Full Text of this article is available as a PDF (514.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
- Jones E. Y., Stuart D. I., Walker N. P. Structure of tumour necrosis factor. Nature. 1989 Mar 16;338(6212):225–228. doi: 10.1038/338225a0. [DOI] [PubMed] [Google Scholar]
- Kriegler M., Perez C., DeFay K., Albert I., Lu S. D. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988 Apr 8;53(1):45–53. doi: 10.1016/0092-8674(88)90486-2. [DOI] [PubMed] [Google Scholar]
- Liu C. C., Detmers P. A., Jiang S. B., Young J. D. Identification and characterization of a membrane-bound cytotoxin of murine cytolytic lymphocytes that is related to tumor necrosis factor/cachectin. Proc Natl Acad Sci U S A. 1989 May;86(9):3286–3290. doi: 10.1073/pnas.86.9.3286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
- Sehajpal P., Subramaniam A., Murthi V. K., Sharma V. K., Suthanthiran M. Demonstration of a direct inhibitory effect of cyclosporine on normal human T-cells with two novel models of T-cell activation as probes. Cell Immunol. 1989 Apr 15;120(1):195–204. doi: 10.1016/0008-8749(89)90187-1. [DOI] [PubMed] [Google Scholar]
- Sherry B., Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses. J Cell Biol. 1988 Oct;107(4):1269–1277. doi: 10.1083/jcb.107.4.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sung S. S., Bjorndahl J. M., Wang C. Y., Kao H. T., Fu S. M. Production of tumor necrosis factor/cachectin by human T cell lines and peripheral blood T lymphocytes stimulated by phorbol myristate acetate and anti-CD3 antibody. J Exp Med. 1988 Mar 1;167(3):937–953. doi: 10.1084/jem.167.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Unglaub R., Maxeiner B., Thoma B., Pfizenmaier K., Scheurich P. Downregulation of tumor necrosis factor (TNF) sensitivity via modulation of TNF binding capacity by protein kinase C activators. J Exp Med. 1987 Dec 1;166(6):1788–1797. doi: 10.1084/jem.166.6.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]