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Publication : Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells.

First Author  Kotsianidis I Year  2006
Journal  Blood Volume  107
Issue  8 Pages  3138-44
PubMed ID  16373666 Mgi Jnum  J:131259
Mgi Id  MGI:3773406 Doi  10.1182/blood-2005-07-2804
Citation  Kotsianidis I, et al. (2006) Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells. Blood 107(8):3138-44
abstractText  Invariant natural killer T cells (iNKT cells) are a small subset of immunoregulatory T cells highly conserved in humans and mice. On activation by glycolipids presented by the MHC-like molecule CD1d, iNKT cells promptly secrete T helper 1 and 2 (Th1/2) cytokines but also cytokines with hematopoietic potential such as GM-CSF. Here, we show that the myeloid clonogenic potential of human hematopoietic progenitors is increased in the presence of glycolipid-activated, GM-CSF-secreting NKT cells; conversely, short- and long-term progenitor activity is decreased in the absence of NKT cells, implying regulation of hematopoiesis in both the presence and the absence of immune activation. In accordance with these findings, iNKT-cell-deficient mice display impaired hematopoiesis characterized by peripheral-blood cytopenias, reduced marrow cellularity, lower frequency of hematopoietic stem cells (HSCs), and reduced early and late hematopoietic progenitors. We also show that CD1d is expressed on human HSCs. CD1d-expressing HSCs display short- and long-term clonogenic potential and can present the glycolipid alpha-galactosylceramide to iNKT cells. Thus, iNKT cells emerge as the first subset of regulatory T cells that are required for effective hematopoiesis in both steady-state conditions and under conditions of immune activation.
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