At present, it is not clear how extracellular Trx1 is regenerated in vivo. Despite the overall oxidizing character of the extracellular compartment, reductive processes are known to take place on the cell surface. On the one hand, there is longstanding evidence for the existence of transplasma membrane redox systems delivering electrons to the cell surface (Crane et al, 1985) . On the other hand, Trx1 may be regenerated by co-secreted reductants, as Trx1 secretion in DC-T co-culture is accompanied by the release of reduced cysteine and the creation of a reducing microenvironment between interacting cells (Angelini et al, 2002) . In addition, TrxR was found to be secreted by activated monocytes and might be part of an extracellular Trx1 reducing system (Soderberg et al, 2000) .