Regulation of anti-HLA antibody-dependent natural killer cell activation by immunosuppressive agents.
Transplantation
; 97(3): 294-300, 2014 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-24342979
ABSTRACT
BACKGROUND:
It was demonstrated that human natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC)-like mechanism, increase IFNγ production after exposure to alloantigens. This finding was associated with an increased risk for antibody-mediated rejection (ABMR). Although the effects of various immunosuppressive drugs on T cells and B cells have been extensively studied, their effects on NK cells are less clear. This study reports the effect of immunosuppressive agents on antibody-mediated NK cell activation in vitro.METHODS:
Whole blood from normal individuals was incubated with irradiated peripheral blood mononuclear cells (PBMCs) pretreated with anti-HLA antibody+ sera (in vitro ADCC), with or without immunosuppressive agents. The %IFNγ+ and CD107a+ (degranulation marker) in CD56+ NK cells were enumerated by flow cytometry.RESULTS:
Cyclosporine A and tacrolimus significantly reduced IFNγ production in a dose-dependent manner (53%-83%), but showed minimal effect on degranulation (20%). Prednisone significantly reduced both IFNγ production and degranulation (50%-66% reduction at maximum therapeutic levels). Calcineurin inhibitors (CNIs) in combination with prednisone additively suppressed IFNγ production and degranulation. The effect of sirolimus or mycophenolate mofetil on NK cells was minimal.CONCLUSIONS:
These results suggest that potent suppressive effects of CNIs and prednisone on antibody-mediated NK cell activation may contribute to the reduction of ADCC in sensitized patients and possibly reduce the risk for ADCC-mediated ABMR. These further underscore the importance of medication compliance in prevention of ABMR and possibly chronic rejection, and suggest that ADCC-mediated injury may increase in strategies aimed at CNI or steroid minimization or avoidance.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Terapia de Inmunosupresión
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Antígenos HLA
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Inmunosupresores
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Anticuerpos
Tipo de estudio:
Etiology_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article