Natural killer (NK) cells reconstitute rapidly following allogeneic stem cell transplantation (allo-SCT) at a time when alloreactive T cell immunity is being established. Important differences are seen in the patterns of reconstitution between T cell deplete, T cell replete and umbilical cord stem cell transplants. 82 patients who received T cell-deplete allo-SCT were studied to determine the functional and transcriptional profile of the reconstituting NK cells and to assess the relationship with clinical outcome. NK cells at day 14 (D14-NK) were donor-derived, intensely proliferating and expressed chemokine receptors targeted to lymphoid and peripheral tissue. Spontaneous production of the immunoregulatory cytokine IL-10 was observed in over 70% of cells and transcription of cytokines and growth factors was augmented. D14-NK cell number was inversely correlated with the incidence of grade II-IV acute graft versus host disease (GVHD). These findings reveal that robust reconstitution of immunoregulatory NK cells by day 14 after allo-SCT is an important determinant of clinical outcome and suggest NK cells may suppress development of the T cell-mediated alloreactive immune response through production of IL-10.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:768280 |
| Date | January 2018 |
| Creators | Chan, Yuen Ling (Tracey) |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/8714/ |
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