defining early human nk cell developmental stages in primary and secondary lymphoid tissues定义早期人类nk细胞发育阶段在初级和次级淋巴组织.pdfVIP

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defining early human nk cell developmental stages in primary and secondary lymphoid tissues定义早期人类nk细胞发育阶段在初级和次级淋巴组织.pdf

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defining early human nk cell developmental stages in primary and secondary lymphoid tissues定义早期人类nk细胞发育阶段在初级和次级淋巴组织

Defining Early Human NK Cell Developmental Stages in Primary and Secondary Lymphoid Tissues 1 2 1 1 2 Diana N. Eissens , Jan Spanholtz , Arnold van der Meer , Bram van Cranenbroek , Harry Dolstra , Jaap 3 2 1 Kwekkeboom , Frank W. M. B. Preijers , Irma Joosten * 1 Department of Laboratory Medicine - Laboratory of Medical Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 2 Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 3 Laboratory of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, The Netherlands Abstract A better understanding of human NK cell development in vivo is crucial to exploit NK cells for immunotherapy. Here, we identified seven distinctive NK cell developmental stages in bone marrow of single donors using 10-color flow cytometry and found that NK cell development is accompanied by early expression of stimulatory co-receptor CD244 in vivo. Further analysis of cord blood (CB), peripheral blood (PB), inguinal lymph node (inLN), liver lymph node (liLN) and spleen (SPL) samples showed diverse distributions of the NK cell developmental stages. In addition, distinctive expression profiles of early development marker CD33 and C-type lectin receptor NKG2A between the tissues, suggest that differential NK cell differentiation may take place at different anatomical locations. Differential expression of NKG2A and stimulatory receptors (e.g. NCR, NKG2D) within the different subsets of committed NK cells demonstrated the heterogeneity of the CD