Solitary pancreas allografts. The role of percutaneous biopsy and standardized histologic grading of rejection

Murine models such as NZB/W F1, NZB.H-2bm12 and MRL.lpr/lpr mice have provided greater insight into the pathogenic mechanisms of lupus. To understand further the roles of T cells and cytokines in the pathogenesis of murine lupus, 11 cloned anti-DNA antibodies augmenting autoreactive T cell lines were derived from NZB/W F1 mice. All these autoreactive cells responded to syngeneic splenic cells and helped syngeneic B cells to produce anti-DNA antibodies, especially the IgG antibody. Ten out of 11 autoreactive T cell lines expressed neither CD4 nor CD8 cell surface markers on their surface. In addition, the cytokine production pattern of these autoreactive T cell lines was predominantly of type 0 (Th0) or type 2 T helper cells (Th2). To further investigate the role of accessory molecules in the activation of these autoreactive T cell lines, expression of IL-2R and heat-stable antigen (HSA) on these autoreactive T cells was analysed. Results suggest that the HSA played a critical role in the activation and function of these double-negative cloned autoreactive T cells.     

Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop

Argos is a secreted molecule with an atypical EGF motif. It was recently shown to function as an inhibitor of the signaling triggered by the Drosophila EGF receptor (DER). In this work, we determine the contribution of Argos to the establishment of cell fates in the embryonic ventral ectoderm. Graded activation of DER is essential for patterning the ventral ectoderm. argos mutant embryos show expansion of ventral cell fates suggesting hyperactivation of the DER pathway. In the embryonic ventral ectoderm, argos is expressed in the ventralmost row of cells. We show that argos expression in the ventral ectoderm is induced by the DER pathway: argos is not expressed in DER mutant embryos, while it is ectopically expressed in the entire ventral ectoderm following ubiquitous activation of the DER pathway. argos expression appears to be triggered directly by the DER pathway, since induction can also be observed in cell culture, following activation of DER by its ligand, Spitz. Argos therefore functions in a sequential manner, to restrict the duration and level of DER signaling. This type of inhibitory feedback loop may represent a general paradigm for signaling pathways inducing diverse cell fates within a population of non-committed cells.