A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells.
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.
Kinkhabwala
M
M
Rogosin Institute, Department of Medicine, Cornell University Medical College, New York, New York 10021.
Sehajpal
P
P
Skolnik
E
E
Smith
D
D
Sharma
V K
VK
Vlassara
H
H
Cerami
A
A
Suthanthiran
M
M
D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008775:Methylprednisolone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000235:genetics
D003524:Cyclosporins; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; D008775:Methylprednisolone