Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells.
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.
Kotsianidis
Ioannis
I
Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, United Kingdom.
Silk
Jonathan D
JD
Spanoudakis
Emmanouil
E
Patterson
Scott
S
Almeida
Antonio
A
Schmidt
Richard R
RR
Tsatalas
Costas
C
Bourikas
George
G
Cerundolo
Vincenzo
V
Roberts
Irene A G
IA
Karadimitris
Anastasios
A
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor