Tumor necrosis factor α mediates a T cell receptor-independent induction of the gene regulatory factor NF-κB 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-κB in T lymphocytes without engagement of the T cell receptor. We found that NF-κB 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 TNFα. The addition of antibody against TNFα blocked the ability of APCs to induce NF-κB. These observations were extended by the finding that NF-κB was also induced in T lymphocytes separated by a membrane from a mixture of T lymphocytes, splenic APCs and antigen by a TNFα-dependent mechanism. Together, these findings suggest that induction of NF-κB in antigenically stimulated or 'bystander' T cells may take place through stimulation by TNFa as well as in response to T cell receptor occupancy.