Identification of an NK/T cell–restricted progenitor in adult bone marrow contributing to bone marrow– and thymic-dependent NK cells

• Published in: Blood Vol. 116; no. 2; pp. 183 - 192
• Main Authors: Nozad Charoudeh, Hojjatollah, Tang, Yanjuan, Cheng, Min, Cilio, Corrado M., Jacobsen, Sten Eirik W., Sitnicka, Ewa
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.07.2010; Americain Society of Hematology
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Cell Differentiation - immunology; Cell Lineage; Cell Separation; Clinical Medicine; Flow Cytometry; Hematologi; Hematologic and hematopoietic diseases; Hematology; Hematopoiesis - immunology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Klinisk medicin; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Multipotent Stem Cells - cytology; Multipotent Stem Cells - immunology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymus Gland - cytology; Thymus Gland - immunology; Human; Natural killer cell; Thymus gland; Natural killer T cell; Hematology; Stem cell; T-Lymphocyte; Bone marrow; Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2009-10-247130

Although bone marrow (BM) is the main site of natural killer (NK)–cell development in adult mice, recent studies have identified a distinct thymic-dependent NK pathway, implicating a possible close link between NK- and T-cell development in adult hematopoiesis. To investigate whether a potential NK-/T-lineage restriction of multipotent progenitors might take place already in the BM, we tested the full lineage potentials of NK-cell progenitors in adult BM. Notably, although Lin−CD122+NK1.1−DX5− NK-cell progenitors failed to commit to the B and myeloid lineages, they sustained a combined NK- and T-cell potential in vivo and in vitro at the single-cell level. Whereas T-cell development from NK/T progenitors is Notch-dependent, their contribution to thymic and BM NK cells remains Notch-independent. These findings demonstrate the existence of bipotent NK-/T-cell progenitors in adult BM.