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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3138-3144.
Prepublished online as a Blood First Edition Paper on December 22, 2005; DOI 10.1182/blood-2005-07-2804.
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Submitted July 14, 2005
Accepted December 13, 2005
Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells
IOANNIS KOTSIANIDIS, JONATHAN D SILK, EMMANOUIL SPANOUDAKIS, SCOTT PATTERSON, ANTONIO ALMEIDA, RICHARD R SCHMIDT, COSTAS TSATALAS, GEORGE BOURIKAS, VINCENZO CERUNDOLO, IRENE A ROBERTS, and ANASTASIOS KARADIMITRIS*
Department of Haematology, Hammersmith Hospital, Imperial College London, London, United Kingdom; Department of Haematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom
Department of Haematology, Hammersmith Hospital, Imperial College London, London, United Kingdom
Department of Chemistry, University of Konstanz, Konstanz, Germany
Department of Haematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
* Corresponding author; email: a.karadimitris{at}imperial.ac.uk.
Invariant NKT cells (iNKT cells) are a small subset of immunoregulatory T cells highly conserved in humans and mice. Upon activation by glycolipids presented by the MHC-like molecule CD1d, iNKT cells promptly secrete 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 both in the presence and 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 (HSC), and reduced early and late hematopoietic progenitors. We also show that CD1d is expressed on human HSC. CD1d-expressing HSC display short- and long-term clonogenic potential and can present the glycolipid  -galactosylceramide to iNKT cells. Thus, iNKT cells emerge as the first subset of regulatory T cells that are required for effective haemopoiesis in both steady state conditions and under conditions of immune activation.
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