Background
T-cell receptor (TCR)-induced IL-2 expression is suppressed at the level of mRNA and protein following chronic culture of T cells with tumour necrosis factor (TNF) at picomolar concentrations, an effect that is reversible upon removal of TNF. This TCR hyporesponsiveness is reminiscent of that of T cells recovered from inflamed sites such as the rheumatoid synovium. We have found that, although chronic TNF attenuates TCRζ expression and TCR-proximal signalling, IL-2 expression is suppressed regardless of whether cells are stimulated via the TCR, or with phorbol ester and calcium ionophore to activate the MAPK and NFAT pathways directly. Suppression therefore occurs independently of TCR-proximal effects of TNF [1, 2].