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Interferon Gamma and Contact-dependent Cytotoxicity Are Each Rate Limiting for Natural Killer Cell-Mediated Antibody-dependent Chronic Rejection.
Lin, C M; Plenter, R J; Coulombe, M; Gill, R G.
Afiliação
  • Lin CM; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Aurora, CO. christine.lin@ucdenver.edu.
  • Plenter RJ; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Aurora, CO.
  • Coulombe M; Department of Surgery, University of Colorado, Aurora, CO.
  • Gill RG; Department of Surgery, University of Colorado, Aurora, CO.
Am J Transplant ; 16(11): 3121-3130, 2016 11.
Article em En | MEDLINE | ID: mdl-27163757
Natural killer (NK) cells are key components of the innate immune system. In murine cardiac transplant models, donor-specific antibodies (DSA), in concert with NK cells, are sufficient to inflict chronic allograft vasculopathy independently of T and B cells. In this study, we aimed to determine the effector mechanism(s) required by NK cells to trigger chronic allograft vasculopathy during antibody-mediated rejection. Specifically, we tested the relative contribution of the proinflammatory cytokine interferon gamma (IFN-γ) versus the contact-dependent cytotoxic mediators of perforin and the CD95/CD95L (Fas/Fas ligand [FasL]) pathway for triggering these lesions. C3H/HeJ cardiac allografts were transplanted into immune-deficient C57BL/6 rag-/- γc-/- recipients, who also received monoclonal anti-major histocompatibility complex (MHC) class I DSA. The combination of DSA and wild-type NK cell transfer triggered aggressive chronic allograft vasculopathy. However, transfer of IFN-γ-deficient NK cells or host IFN-γ neutralization led to amelioration of these lesions. Use of either perforin-deficient NK cells or CD95 (Fas)-deficient donors alone did not alter development of vasculopathy, but simultaneous disruption of NK cell-derived perforin and allograft Fas expression resulted in prevention of these abnormalities. Therefore, both NK cell IFN-γ production and contact-dependent cytotoxic activity are rate-limiting effector pathways that contribute to this form of antibody-induced chronic allograft vasculopathy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Linfócitos T Citotóxicos / Transplante de Coração / Interferon gama / Rejeição de Enxerto / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2016 Tipo de documento: Article País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Linfócitos T Citotóxicos / Transplante de Coração / Interferon gama / Rejeição de Enxerto / Anticorpos Monoclonais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2016 Tipo de documento: Article País de publicação: Estados Unidos