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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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HEMATOPOIESIS

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. G. Roberts, and Anastasios Karadimitris

From the Department of Haematology, Hammersmith Hospital, Imperial College London, United Kingdom; the Department of Haematology, Democritus University of Thrace Medical School, Alexandroupolis, Greece; the Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom; and the Department of Chemistry, University of Konstanz, Germany.

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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