INFLUENCE OF ISLET TRANSPORTATION ON PANCREATIC ISLET ALLOTRANSPLANTATION IN TYPE 1 DIABETIC PATIENTS WITHIN THE SWISS-FRENCH GRAGIL NETWORK

The influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients was evaluated within the GRAGIL network.From December 2001 to April 2003, 16 human pancreatic islet transplants were performed in 9 type 1 diabetic patients with an established kidney graft (functioning for at least 6 months) in four centers of the GRAGIL network. Islet isolation was performed in a core laboratory in Geneva, and the islet preparations were shipped by ambulance to each center for transplantation. One month after transplantation, the efficiency of the graft was assessed according to islet transportation time (ITT): ITT less than 2 hours (group 1, n=5), and ITT greater tha…

Expression séquentielle du TGFβ1 et de son récepteur de type 1 selon la pathologie initiale du transplant rénal. Relation avec la néphropathie chronique de l’allogreffe ?

But du travail La nephropathie chronique de l’allogreffe (NCA) qui se traduit cliniquement par un dysfonctionnement chronique du transplant renal, reste la principale cause de perte tardive du transplant renal. Ses mecanismes sont multiples et encore mal compris. Le but de ce travail est d’etudier l’expression du TGFβ1 et de son recepteur de type 1 en fonction de la pathologie initiale et de rechercher un lien avec la NCA. Materiel et methodes Trente quatre transplantes renaux ont ete inclus dans cette etude. Les biopsies du transplant renal, realisees lors de dysfonctionnement ou a titre systematique ont ete classees, selon le delai ecoule apres la transplantation, en biopsie precoces (del…

Injection of Donor-Derived OX62+ Splenic Dendritic Cells With Anti-CD4 Monoclonal Antibody Generates CD4+CD25+FOXP3+ Regulatory T Cells That Prolong Allograft Skin Survival Indefinitely and Abrogate Production of Donor-Specific Antibodies in a Rat Model

Abstract Objective To examine in a rat model the ability of donor dendritic cells and anti-CD4 monoclonal antibody (mAb) to generate donor-specific CD4+CD25+ regulatory T cells (Tregs) and to evaluate the capacity of these Tregs to prolong skin allograft survival and abrogate the production of donor-specific antibodies after skin grafting. Materials and Methods OX62+ (nonplasmacytoid) splenic dendritic cells were isolated from Fischer rats using magnetic beads and injected (2 × 10 6 ) into Lewis rat recipients with or without treatment with a nondepleting anti-CD4 (W3/25) mAb. After 4 weeks, splenic CD4+CD25+FOXP3+ T cells were harvested using magnetic beads from conditioned animals and inj…

In vitro study of alloreactivity and microchimerism after injection of dendritic cells and anti-CD4 monoclonal antibody in a combination of Lewis-Wistar Furth rats: preliminary data.

Antibodies to vascular endothelial cells in chronic rejection of renal allografts.

Injection of donor-derived splenic dendritic cells plus a nondepleting anti-CD4 monoclonal antibody to prolong primary skin graft survival indefinitely and abrogate the production of donor-specific antibodies in the Fischer-to-Lewis rat combination.

Abstract We have previously shown that injection of donor-derived Fischer rat OX62+ dendritic cells plus an anti-CD4 monoclonal antibody generates donor-specific CD4+CD25+FoxP3+ regulatory T cells in Lewis rats spleens. The regulatory T cells indefinitely prolonged the survival of skin graft from Fischer rat and abrogated the antidonor antibody response. We have now shown that an injection of 2 × 10 6 donor-derived OX62+ dendritic cells plus 2 mg nondepleting anti-CD4 monoclonal antibody (W3/25) at 28 days before grafting induced indefinite skin graft survival in this combination; whereas an injection on day −1 prolonged it only to 50 days. This effect is donor specific. In both cases, we s…

Extracorporeal circuit heparinization in selective low density lipoprotein apheresis: changes in patient hemostasis and low molecular weight heparin benefit.

Treatment by low density lipoprotein (LDL) apheresis using dextran sulfate columns (DSC) leads to hemostasis alterations with prolonged activated partial thromboplastin time (APTT) of more than 120 seconds. In order to explain this hypocoagulability, we studied hemostasis parameters both in patients and in the extracorporeal circulation (ECC). Hemostasis changes are first related to unfractionated heparin (UFH)—needed to avoid circuit coagulation—which leads to high residual heparinemia in the patient (more than 3 times the recommended level for therapeutic use). Second, the hypocoagulability is induced by a coagulation factor decrease (primarily factors V, VIH, and X) mainly due to an adso…

Regulatory (suppressor) T cells in peripheral allograft tolerance and graft-versus-host reaction.

Among the mechanisms capable of inducing peripheral tolerance, regulatory (suppressor) T cells (Treg) probably play a key role in the control of both reactivity to self-antigens and alloimmune response. Augmentation or manipulation of Treg could improve organ allograft survival or control graft-versus-host disease, thus resulting in operational tolerance. The role of this immunomanipulation as one method of inducing tolerance has yet to be clearly defined.