Given its influence on ligand binding, we reasoned that Trx1 might interfere with CD30-mediated signaling. To test whether Trx1-mediated conformational alteration of CD30 affects CD30-dependent cellular responses, we made use of the YT large granular lymphoma line that has previously been used to study signals emanating from CD30 and to define the genes regulated by such signals (Muta et al, 2000) . Consistent with previous results (Bowen et al, 1993) , we observed that stimulation of CD30 with either agonistic antibodies or sCD30L led to upregulation of the IL-2Ra chain (CD25) within 24 h ( Figure 7A , lower panel, compare columns 3, 4 and 7). Treatment of YT cells with Trx1(CCAAA) (but not with redox-inactive Trx1) prevented CD25 upregulation ( Figure 7A , lower panel, columns 5 and 8), concomitant with the redox change in CD30 ( Figure 7A , upper panel, column 4), thus demonstrating that the redox interaction between Trx1 and CD30 has a pronounced influence on CD30-mediated gene expression.