The biological features and clinical significance of natural killer cell reconstitution following allogenic stem cell transplantation

[摘要] 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.

[发布机构] University:University of Birmingham;Department:Institute of Immunology and Immunotherapy

[关键词] Q Science;QR Microbiology;QR180 Immunology