Expression of TNF-related apoptosis-inducing ligand (TRAIL) in keratinocytes mediates apoptotic cell death in allogenic T cells

Members of the TNF ligand family control and conduct numerous immunological and inflammation-related reactions. The Fas-FasL system and its associated mechanism of activation-induced cell death play an important role for the maintenance of hemostasis of the lymphoid system and the induction of immune tolerance [1]. The TNF-related apoptosis-inducing ligand (TRAIL) was identified as a homologue of the Fas-ligand (FasL) [2]. Yet, in contrast to FasL, TRAIL expression has been demonstrated in various tissues and organs [2-4], as the expression pattern of TRAIL receptors allows a subtle observation of apoptotic reactions. Until now, five different receptors for TRAIL have been described and all belong to the TNF receptor family. The receptors TRAIL-R1/DR4, TRAIL-R2/DR5, TRAIL-R3/DcR1 and TRAIL-R4/DcR2 exhibit a considerably homologous sequence of their extracellular domain and bind TRAIL as the only known ligand. The soluble receptor osteoprotegerin (OPG) belongs to a different sub-family and binds the ligand RANKL/OPGL as well. Following ligand binding and activation of cytoplasmatic death domains, TRAIL-R1 and TRAIL-R2 start series of signals for apoptosis [4,5], whereas the decoy receptors do not transmit death signals. The ratio of expression of DR4/DR5 and decoy receptors by a tumor cell will determine its sensibility for TRAIL-induced apoptosis [2,4]. An important function of TRAIL is the regulation of the immune response being involved in controlling the extent of the activated lymhocyte reaction [6]. Interactions between TRAIL and lymphocytes can create so-called immune-privileged sites, e.g. the placenta [7].The use of TRAIL for the induction of tolerance against allogenic transplants should be considered in burn medicine. The therapy of massive burn injuries is highly complex and can result in grave personal and socio-economic consequences. The therapeutic gold standard is the early resection of necrotic tissue and subsequent wound coverage with autologous ski