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- Corbascio, Matthias, et al.
(författare)
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Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice.
- 2002
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Ingår i: Transplantation. - 1534-6080. ; 74:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L-/- mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L-/-) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart transplantation. To overcome CD40L-independent immune responses, we used anti-lymphocyte function-associated antigen monoclonal antibody (LFA)-1, which has previously been shown to inhibit CD8+ immune responses. METHODS: We conducted mixed lymphocyte reactions, cytotoxicity assays, skin transplantation, and vascularized heterotopic heart transplantation in wild-type B6 and CD40L-deficient mice in the presence and absence of anti-LFA-1 to study the effects of anti-LFA-1 in the absence of CD40L signaling. RESULTS: Anti-LFA-1 inhibited proliferation of naïve CD40L-/- mixed leukocyte reactions and the lysis of donor targets by CD40L-/- cytotoxic T lymphocytes. Anti-LFA-1-treated CD40L-/- mice that received fully MHC-mismatched skin grafts showed significant prolongation of graft survival, with a median survival time of 55 days (mean 66 days) compared with 13 and 21 days in wild-type and CD40L-/- controls, respectively. CD40L-/- mice that received fully MHC-mismatched vascularized heart transplants treated with four doses of 200 microg of anti-LFA-1 at the time of transplantation did not develop any signs of chronic vasculopathy 150 days after transplantation. CONCLUSION: These results indicate that anti-LFA-1 can complement CD40L inhibition in the prevention of undesirable immune responses.
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- Hubberten, HW, et al.
(författare)
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The periglacial climate and environment in northern Eurasia during the Last Glaciation
- 2004
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1333-1357
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Forskningsöversikt (refereegranskat)abstract
- This paper summarizes the results of studies of the Late Weichselian periglacial environments carried out in key areas of northern Eurasia by several QUEEN teams (European Science Foundation (ESF) programme: "Quaternary Environment of the Eurasian North"). The palaeoglaciological boundary conditions are defined by geological data on timing and extent of the last glaciation obtained in the course of the EU funded project "Eurasian Ice Sheets". These data prove beyond any doubt, that with the exception of the northwestern fringe of the Taymyr Peninsula, the rest of the Eurasian mainland and Severnaya Zemlya were not affected by the Barents-Kara Sea fee Sheet during the Last Glacial Maximum (LGM). Inversed modelling based on these results shows that a progressive cooling which started around 30 ka BP, caused ice growth in Scandinavia and the northwestern areas of the Barents-Kara Sea shelf, due to a maritime climate with relatively high precipitation along the western flank of the developing ice sheets. In the rest of the Eurasian Arctic extremely low precipitation rates (less than 50 mm yr(-1)), did not allow ice sheet growth in spite of the very cold temperatures. Palaeoclimatic and palaeoenvironmental conditions for the time prior to, during, and after the LGM have been reconstructed for the non-glaciated areas around the LGM ice sheet with the use of faunal and vegetation records, permafrost, eolian sediments, alluvial deposits and other evidences. The changing environment, from interstadial conditions around 30 ka BP to a much colder and drier environment at the culmination of the LGM at 20-15 ka BP, and the beginning of warming around 15 ka BP have been elaborated from the field data, which fits well with the modelling results. (C) 2003 Elsevier Ltd. All rights reserved.
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- Kjaer, Kurt, et al.
(författare)
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Mezen Bay - a key area for understanding Weichselian glaciations in northern Russia
- 2003
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Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 18:1, s. 73-93
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Tidskriftsartikel (refereegranskat)abstract
- Sediment successions in coastal cliffs around Mezen Bay, southeastern White Sea, record an unusually detailed history of former glaciations, interstadial marine and fluvial events from the Weichselian. A regional glaciation model for the Weichselian is based on new data from the Mezen Bay area and previously published data from adjacent areas. Following the Mikulinian (Eemian) interglacial a shelf-centred glaciation in the Kara Sea is reflected in proglacial conditions at 100-90 ka. A local ice-cap over the Timan ridge existed between 75 and 65 ka. Renewed glaciation in the Kara Sea spread southwestwards around 60 ka only, interrupted by a marine inundation, before it advanced to its maximum position at about 55-50 ka. After a prolonged ice-free period, the Scandinavian ice-sheet invaded the area from the west and terminated east of Mezen Bay about 17 ka. The previously published evidence of a large ice-dammed lake in the central Arkhangelsk region, Lake Komi, finds no support in this study. Copyright (C) 2003 John Wiley Sons, Ltd.
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