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• W1977622017 abstract "T cell depleting strategies are an integral part of immunosuppressive regimens widely used in the hematological and solid organ transplant setting. Although it is known to induce lymphocytopenia, little is known about the effects of the polyclonal rabbit antithymocyte globulin (rATG) or the monoclonal anti-CD52 antibody alemtuzumab on Natural Killer (NK) cells in detail. Here, we demonstrate that induction therapy with rATG following kidney/pancreas transplantation results in a rapid depletion of NK cells. Treatment of NK cells with rATG and alemtuzumab in vitro leads to impairment of cytotoxicity and induction of apoptosis even at a 10-fold lower concentration (0.1 µg/ml) compared with T and B cells. By generating Fc-parts of rATG and alemtuzumab we illustrate that their ligation to FcγRIII (CD16) is sufficient for the significant induction of degranulation, apoptosis and inflammatory cytokine release (FasL, TNFα and IFNγ) exclusively in CD3−CD56dim NK cells whereas application of rATG and alemtuzumab F(ab) fragments abolishes these effects. These findings are of general importance as our data suggest that NK cells are also mediators of the clinically relevant cytokine release syndrome and that their targeting by therapeutic antibodies should be considered as they are functionally relevant for the effective clearance of opportunistic viral infections and anti-tumor activity posttransplantation." @default.
• W1977622017 created "2016-06-24" @default.
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• W1977622017 date "2009-03-05" @default.
• W1977622017 modified "2023-10-12" @default.
• W1977622017 title "Targeting of Natural Killer Cells by Rabbit Antithymocyte Globulin and Campath-1H: Similar Effects Independent of Specificity" @default.
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• W1977622017 doi "https://doi.org/10.1371/journal.pone.0004709" @default.
• W1977622017 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2651595" @default.
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