Human natural killer cells undergoing in vivo differentiation after allogeneic bone marrow transplantation: analysis of the surface expression and function of activating NK receptors

Patients undergoing allogeneic bone marrow transplantation (BMT) offer a unique system to analyze the NK cell development in vivo. We analyzed NK cells from 24 such patients to assess the acquisition of activating receptors. Five patients displayed an immature NK cell surface phenotype at engraftment, as they were CD16−, KIRs− and NKG2D− while expressed low levels of NKp46, NKp30, 2B4 and NKG2A. These NK cells had particularly low cytolytic activity against the HLA-class I-negative melanoma F01 cell line and the 721.221 Epstein-Barr virus (EBV)B-infected cells. Moreover, cytoxicity was inhibited upon mAb-mediated crosslinking of 2B4. Analysis of NK cells at day 30 after BMT revealed the occurrence of both phenotypic and functional maturation. These data are in agreement with a previous in vitro study showing that immature NK cell precursors express CD16, NKGD2 and killer Ig-like receptors (KIR) only at a late stage of differentiation and also express inhibitory 2B4. Remarkably, one of these patients did not display any phenotypic and functional maturation of NK cells and experienced a fatal post transplant EBV-related lymphoproliferative disease. Our present study allows a better understanding of the NK cell differentiation in vivo.