Patterns of virus-immune T-cell responsiveness. Comparison of (H-2(k) x H-2(b)) {arrow} H-2(b) Radiation Chimeras and negatively selected H-2(b) lymphocytes

Negatively selected H-2K(b)D(b) TDL can be induced to respond strongly to vaccinia virus presented in the context of both H-2K(k) and H-2D(b) when stimulated in irradiated H-2K(k)D(b) recipients. Addition of excess (H- 2K(k)D(b) x H-2K(b)D(b))F1 TDL, which are low responders to H-2D(b)-vaccinia virus, does not obviously suppress the reactivity pattern of the H-2K(b)D(b) T cells. However, lymphocytes from chimeras made by reconstituting H- 2K(b)D(b) mice with (H-2K(k)D(k) × H-2K(b)D(b))F(l) bone marrow cells make little, if any, cytotoxic T-cell response to vaccinia virus when sensitized in H-2K(k)D(b) recipients. We have thus documented one instance where the responder phenotype of T ceils from an F(l) {arrow} parent chimera is not equivalent to that associated with the H-2 type of the parental thymus. Lymphocytes from both the chimera and the H-2K(b)D(b) parent (after negative selection) are tolerant to the H-2K(k) and I-A(k) alloantigens encountered in the recipient, but the chimera T cells are also defective in their response to a neoantigen (vaccinia virus) presented in the context of H-2K(k) which the parental T cells invariably recognize. It is thus possible that at least part of the phenomenology associated with the F(l) {arrow} parent radiation chimeras reflects deletion of repertoire in the context of H-2 antigens present during thymocyte ontogeny on other than radiation-resistant thymic epithelium.     

Transjugular intrahepatic portosystemic shunt-placement increases arginine/asymmetric dimethylarginine ratio in cirrhotic patients

AIM：To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt（TIPS）.METHODS：To determine arginine,asymmetric dimethylarginine（ADMA）,symmetric dimethylarginine（SDMA）,and nitric oxide（NO） plasma levels,blood samples were collected from the superior cava,hepatic,and portal vein just before,directly after,and 3 mo after TIPS-placement.RESULTS：A significant increase in the arginine/ADMA ratio after TIPS placement was shown.Moreover,TIPS placement enhanced renal function and thereby decreased systemic SDMA levels.In patients with renal dysfunction before TIPS placement,both the arginine/ADMA ratio and creatinine clearance rate increased significantly,while this was not the case in patients with normal renal function before TIPS placement.Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION：The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability.In addition,this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase（DDAH） activity and confirms the major role of the liver as an ADMA clearing organ.     

The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhesion structures

Previous studies have shown that human endothelial cells (ECs) adhere to fibrinogen (fg) and fibronectin (fn) and organize their cytoskeleton on these substrata. However, the mechanism governing this chain of events is poorly known. In ECs glycoproteins immunologically and biochemically similar to the platelet membrane GpIIb-IIIa complex have been described. The functional role of this complex in ECs remains to be established. In this study we show that the antigens recognized by polyclonal antibodies raised against human platelet GpIIb-IIIa and crossreacting with the EC form have a discrete and well-organized distribution at cell adhesion structures. Indeed these antigens are located at vinculin-rich focal contacts found at the membrane insertion of microfilament bundles of the stress fiber type. They are also found at cell-to-cell contacts and, with a diffuse pattern, at the dorsal surface of ECs. GpIIb-IIIa antibodies, added to EC suspensions prior to plating, inhibit EC spreading on fg and vitronectin (vn) substrata in a concentration-dependent way. In contrast, the antibodies are very poorly active when the cells are seeded on fn-coated glass. The same antibodies, added to adherent cells, disrupt cell-to-cell contacts and cause their rounding and detachment. Overall these results indicate that EC GpIIb-IIIa complex is involved in controlling the adhesion mechanism of these cells to extracellular matrix proteins.