Inhibition of Notch signaling biases rat thymocyte development towards the NK cell lineage.
Notch receptors are involved in directing the choice between alternative cell fates in developmental scenarios such as thymopoiesis. By pharmacological interference in rat fetal thymus organ culture we show that inhibition of Notch signaling arrests T cell development at an early double-negative stage and is accompanied by a dramatic increase in the number of NK cells. These cells show an activated phenotype, lack recombination of the TCR beta gene locus and express perforin. Similarly, in thymic lobes reconstituted with fetal liver cells, progenitors predominantly develop into NK cells both after pharmacological interference of Notch and after treatment with a recombinant rat Notch1/Fc chimera. Collectively, this identifies the lineage decision of NK/T precursor cells as an important site of Notch action in rat thymocytes.
van den Brandt
Jens
J
Institute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Voss
Katrin
K
Schott
Melanie
M
Hünig
Thomas
T
Wolfe
Michael S
MS
Reichardt
Holger M
HM
D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D010450:Endopeptidases / Q000187:drug effects; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051381:Rats; D051880:Receptors, Notch; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism*; D014280:Triglycerides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000954:Antigens, Surface; D037181:Lectins, C-Type; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051880:Receptors, Notch; D014280:Triglycerides; D005680:gamma-Aminobutyric Acid; C057077:1,2-dilinolenoyl-3-(4-aminobutyryl)propane-1,2,3-triol; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases