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• W2740542012 abstract "Introduction: Integrins play a central role during T cell activation. Stimulation of the T cell receptor results in the activation of the integrin LFA-1 (CD11a/CD18), which in turn binds to the adhesion molecules ICAM-1 and ICAM-2 and promotes effective T cell activation. T cell receptor-mediated integrin activation is mediated by the »Adhesion and Degranulation Promoting Adapter Protein« (ADAP; formerly termed SLAP-130 and Fyb), and is prevented in ADAP-deficient mice [1]. Aim of the presented experiments was to determine the relevance of ADAP for the rejection of allogeneic heart grafts in a mouse model. Material and Methods: ADAP-deficient and wild type (WT) mice on the C57Bl/6 background were kindly provided by Gary Koretzky, Philadelphia. Heart grafts from BALB/c donors were heterotopically grafted to the aorta and V. cava of ADAP-deficient (ADAP-/-) and WT recipients. Heart grafts were harvested at different time points, and cryostat sections were stained with hematoxylin/eosin. At day 8 after transplantation the number of proliferating cells in heart grafts was determined by Bromo-deoxy-Uridine (BrdU) incorporation and subsequent immuno histochemistry. In vitro mixed lymphocyte reactions were performed using CFSE-labelled cells from mesenteric and peripheral lymph nodes of ADAP-deficient and WT-mice that were stimulated by allogeneic BALB/c dendritic cells. The number of cell divisions was determined by flow cytometry. Results: Whereas wild type control mice rejected allogeneic BALB/c heart grafts within a mean of 10.4 days (n = 8), graft survival in ADAP-/- deficient mice was prolonged to a mean of 25.2 days (n = 10). Histological and immunohistological analyses at day 8 after transplantation showed reduced infiltration of mononuclear cells in ADAP-deficient compared to wild type recipients. The number of BrdU-positive cells in the grafts of ADAP-/- recipients was lower than in WT recipients. In vitro ADAP-/- mice showed a slower and reduced proliferative response to allogeneic stimulation. Conclusion: Our results show that T cell receptor-mediated integrin activation by the »Adhesion and Degranulation promoting Adaptor Protein« (ADAP) plays an important role during the alloreactive immune response. Therefore, ADAP could be a novel and interesting target for targeting the induction phase of the immune response following organ trans" @default.
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• W2740542012 date "2006-01-01" @default.
• W2740542012 modified "2023-09-27" @default.
• W2740542012 title "Verlängerung des Transplantatüberlebens durch Inaktivierung der T Zellrezeptor-vermittelten Integrinaktivierung in ADAP-defizienten Mäusen Prolongation of Allograft Survival by Inactivation of T Cell Receptor-mediated Integrin Activation in ADAP-deficient Mice" @default.
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