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Specialized Roles of Human Natural Killer Cell Subsets in Kidney Transplant Rejection.
Kildey, Katrina; Francis, Ross S; Hultin, Sebastian; Harfield, Michelle; Giuliani, Kurt; Law, Becker M P; Wang, Xiangju; See, Emily J; John, George; Ungerer, Jacobus; Wilkinson, Ray; Kassianos, Andrew J; Healy, Helen.
Affiliation
  • Kildey K; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
  • Francis RS; Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
  • Hultin S; Princess Alexandra Hospital, Brisbane, QLD, Australia.
  • Harfield M; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
  • Giuliani K; Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
  • Law BMP; Princess Alexandra Hospital, Brisbane, QLD, Australia.
  • Wang X; Princess Alexandra Hospital, Brisbane, QLD, Australia.
  • See EJ; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
  • John G; Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
  • Ungerer J; Medical School, University of Queensland, Brisbane, QLD, Australia.
  • Wilkinson R; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
  • Kassianos AJ; Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
  • Healy H; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
Front Immunol ; 10: 1877, 2019.
Article in En | MEDLINE | ID: mdl-31440252
Background: Human natural killer (NK) cells are key functional players in kidney transplant rejection. However, the respective contributions of the two functionally distinct human NK cell subsets (CD56bright cytokine-producing vs. CD56dim cytotoxic effector) in episodes of allograft rejection remain uncertain, with current immunohistochemical methods unable to differentiate these discrete populations. We report the outcomes of an innovative multi-color flow cytometric-based approach to unequivocally define and evaluate NK cell subsets in human kidney allograft rejection. Methods: We extracted renal lymphocytes from human kidney transplant biopsies. NK cell subsets were identified, enumerated, and phenotyped by multi-color flow cytometry. Dissociation supernatants were harvested and levels of soluble proteins were determined using a multiplex bead-based assay. Results were correlated with the histopathological patterns in biopsies-no rejection, borderline cellular rejection, T cell-mediated rejection (TCMR), and antibody-mediated rejection (AMR). Results: Absolute numbers of only CD56bright NK cells were significantly elevated in TCMR biopsies. In contrast, both CD56bright and CD56dim NK cell numbers were significantly increased in biopsies with histopathological evidence of AMR. Notably, expression of the activation marker CD69 was only significantly elevated on CD56dim NK cells in AMR biopsies compared with no rejection biopsies, indicative of a pathogenic phenotype for this cytotoxic NK cell subset. In line with this, we detected significantly elevated levels of cytotoxic effector molecules (perforin, granzyme A, and granulysin) in the dissociation supernatants of biopsies with a histopathological pattern of AMR. Conclusions: Our results indicate that human NK cell subsets are differentially recruited and activated during distinct types of rejection, suggestive of specialized functional roles.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transplantation Immunology / Killer Cells, Natural / Lymphocyte Subsets / Kidney Transplantation / Graft Rejection Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Front Immunol Year: 2019 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transplantation Immunology / Killer Cells, Natural / Lymphocyte Subsets / Kidney Transplantation / Graft Rejection Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Front Immunol Year: 2019 Document type: Article Affiliation country: Country of publication: