title: NK cell maturation to CD56(dim) subset associated with high levels of NCRs overrides the inhibitory effect of NKG2A and recovers impaired NK cell cytolytic potential after allogeneic hematopoietic stem cell transplantation.
abstract: NK cell cytotoxicity against residual leukemic cells is crucial for immune system reconstitution after hematopoietic stem cell transplantation (HSCT). Since immune recovery after transplant still remains a major concern, we studied the counterbalance of NK cell receptors after HSCT and its importance in NK cell functional recovery. We investigated NK cell reconstitution in 27 acute leukemia patients at different time points following HLA-matched allogeneic HSCT compared to those of donors. NK cells were evaluated for their cytotoxicity in a standard (51)Cr-release assay against target cells and also analyzed for their receptors expression using flow cytometry. Early after transplant, we found higher percentage of CD56(bright) NK cells, increased levels of NKG2A and NCRs as well as decreased levels of KIRs expression on NK cells associated with an impaired cytotoxicity of these cells. All the abnormalities were normalized by one year after HSCT when CD56(bright) NK cells gradually differentiated into CD56(dim) subset. Collectively, we confirmed a gradual increase of CD56(dim) NK cells expressing NCRs with the significant decrease in NKG2A expression on NK cells. This finding was also associated with the recovery of NK cell cytotoxicity that suggests an important role for the kinetics of NK cell receptors during cell maturation in HSCT outcome.
authors: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
authors: Mehran
authors: M
authors: Ghasemzadeh
authors: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Alfred Medical Research and Education Precinct, Department of Immunology, Monash University, Melbourne, Australia. Electronic address: e.hosseini10@yahoo.com.au.
authors: Ehteramolsadat
authors: E
authors: Hosseini
authors: Department of Hematology and Oncology, Eastern School, Monash University, Melbourne, Australia.
authors: Anthony P
authors: AP
authors: Schwarer
authors: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran; Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: Ali Akbar
authors: AA
authors: Pourfathollah
mesh_terms: D000208:Acute Disease; D064591:Allografts; D019002:CD56 Antigen / Q000276:immunology*; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D007938:Leukemia / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D020127:Recovery of Function / Q000276:immunology*; D061349:Unrelated Donors
chemical_list: D019002:CD56 Antigen; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D009363:Neoplasm Proteins
keywords: CD56(bright); CD56(dim); HSCT; NCRs; NK cell; NKG2A; Reconstitution