Showing papers by "Daniel Graf published in 1995"
TL;DR: Evidence is provided that activated T cells not only express cell membrane‐associated TRAP but also a soluble form of TRAP (sTRAP), which has the potential to be biologically active not only in a transmembrane form but also as a soluble molecule.
Abstract: TRAP is a tumor necrosis factor (TNF)-related, 33-kDa type II transmembrane protein almost exclusively expressed on the surface of activated CD4+ T lymphocytes. Interaction of TRAP with CD40 on B cells is of paramount importance for immunoglobulin class switching and subsequent synthesis of IgG, IgA or IgE in vivo. We now provide evidence that activated T cells not only express cell membrane-associated TRAP but also a soluble form of TRAP (sTRAP). After generating monoclonal antibodies against TRAP and establishing a TRAP-specific enzyme-linked immunosorbent assay we were able to detect substantial amounts of sTRAP in the supernatants of activated T cells. The onset and rate of sTRAP release was found to parallel the expression of TRAP on the cell surface. sTRAP, an 18-kDa protein, is generated by proteolytic processing of full-length TRAP in an intracellular compartment. Starting with methionine 113 of full-length TRAP, sTRAP lacks the transmembrane region and a part of the extracellular domain but contains the entire TNF-alpha homology region and can, therefore, bind to CD40. Like other members of the TNF superfamily (e.g. TNF-alpha, Fas/APO-1 ligand), TRAP thus has the potential to be biologically active not only in a transmembrane form but also as a soluble molecule.
261 citations
TL;DR: Results show that mLC spontaneously undergo apoptosis in culture and that the progression of mLC to apoptosis is inhibited by TRAP and TNF‐α, but accelerated by IL‐10.
Abstract: In the lymphoid tissues, adaptive immune responses are initiated by the interaction of interdigitating dendritic cells (IDC) with naive T cells. To understand this interplay better, we used mature Langerhans cells (mLC), migrating from human epidermis, as the correlate of IDC ex vivo to evaluate the different effects of tumor necrosis factor (TNF)-alpha. TNF-related activation protein (TRAP; CD40-ligand) and interleukin-10 (IL-10) on induction or prevention of apoptotic cell death in these cells. Spontaneous decrease of mLC viability in culture was due to apoptosis, as determined by the appearance of typical morphological changes such as dilatation of the endoplasmic reticulum (ER), chromatin condensation and membrane blebbing. IL-10 strongly reduced mLC viability, whereas TRAP and TNF-alpha facilitated the survival of mLC. Spontaneous DNA fragmentation was detectable after 24 h in culture. IL-10 led to an earlier onset of DNA fragmentation, whereas TRAP and TNF-alpha delayed internucleosomal DNA cleavage. We found that IL-10-treated mLC were readily ingested and removed by macrophages. TNF-alpha and TRAP, in contrast, reduced engulfment of mLC by macrophages. Interestingly, IL-10, even at low concentrations, reverted the effects of TNF-alpha and TRAP in inhibiting mLC apoptosis. Furthermore, IL-10 led to the down-regulation of various surface antigens, especially of CD86 and CD54, whereas TNF-alpha and TRAP enhanced the expression of MHC class I and II antigens and of the accessory molecules CD40, CD54, CD80 and CD86. Taken together, these results show that mLC spontaneously undergo apoptosis in culture and that the progression of mLC to apoptosis is inhibited by TRAP and TNF-alpha, but accelerated by IL-10.
236 citations