CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response.

T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response. Cross-linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF-alpha. Reverse signaling of CD137L also mediates migration of DC via up-regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP-3beta-dependent SCID mouse migration model. Finally, CD137L-activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L-activated DC in an antigen-specific reaction leads to T cell proliferation and the release of IL-12p70 and IFN-gamma. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen-specific T cell differentiation.

A new storage solution for porcine aortic valves.

The aim of this study was to assess the calcification tendency of two biovalves manufactured by different fixation techniques and compare their biocompatibility when implanted subcutaneously in rats. Two biological valve types (Intact) and Mosaic, stored in either glutaraldehyde or in a solution recently developed in our department, were investigated ultrastructurally and their calcium content was measured following 12 weeks subcutaneous implantation in rats. All valves tested in this study showed a considerable loss of the endothelial cover, as judged by scanning electron microscopy. Independent of fixation conditions, the bioprostheses demonstrated a partial destruction of collagen fibers and a rearrangement of the extracellular matrix. The calcium content of Intact valves was significantly higher than that of Mosaic valves (66+/-2.6 versus 3.6+/-0.6 mg/g dry tissue, p<0.0001). Low calcium content of the bioprostheses is considered to result from effective anti-calcification treatment. Ultrastructural changes of prosthetic tissue seem to promote degenerative calcification. The valves stored in the new storage solution exhibited a calcium content which was reduced by approximately 50% compared to those stored in glutaraldehyde. The percentage of reduction in calcification of the valves stored in our newly developed solution is independent of the fixation conditions (p=0.886). The advantage of the new storage solution is based on the fact that rinsing is unnecessary before implantation and, most importantly, a clear reduction in the calcification tendency is achieved.