Tumor necrosis factor alpha mediates a T cell receptor-independent induction of the gene regulatory factor NF-kappa B in T lymphocytes.
We investigated the molecular basis of the ability of DCEK experimental antigen-presenting cells (APCs) to induce the nuclear form of the transcription factor NF-kappa B in T lymphocytes without engagement of the T cell receptor. We found that NF-kappa B induction did not require contact between the APCs and T lymphocytes and could be achieved by medium conditioned by the APCs. The APCs were found to express low levels of mRNA for TNF alpha. The addition of antibody against TNF alpha blocked the ability of APCs to induce NF-kappa B. These observations were extended by the finding that NF-kappa B was also induced in T lymphocytes separated by a membrane from a mixture of T lymphocytes, splenic APCs and antigen by a TNF alpha-dependent mechanism. Together, these findings suggest that induction of NF-kappa B in antigenically stimulated or 'bystander' T cells may take place through stimulation by TNF alpha as well as in response to T cell receptor occupancy.
Grilli
M
M
Laboratory of Immunology, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Chen-Tran
A
A
Lenardo
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D002999:Clone Cells; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D009841:Oligonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D017077:Culture Media, Conditioned; D016328:NF-kappa B; D009841:Oligonucleotides; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha