title: A unique lymphotoxin {alpha}beta-dependent pathway regulates thymic emigration of V{alpha}14 invariant natural killer T cells.
abstract: Natural killer (NK) T cells using an invariant Valpha14 (Valpha14i) T cell receptor rearrangement form a distinct immunoregulatory T cell lineage. Several studies indicated that a NK1.1(-) Valpha14i NKT precursor cell differentiates and expands within the thymus before export to the peripheral tissues occurs. However, little is known about the signals that cause the emigration of Valpha14i NKT cells from the thymus to the periphery. Here we show that signaling of lymphotoxin (LT) alphabeta through the LTbeta receptor (LTbetaR) is indispensable for regulating peripheral but not thymic Valpha14i NKT cell numbers. Homing to and homeostatic proliferation of thymic Valpha14i NKT cells in peripheral organs, however, was not dependent on LTbetaR. Instead, our data indicate that a LTbetaR-expressing thymic stromal cell regulates the thymic emigration of Valpha14i NKT cells but not conventional T cell receptor alphabeta cells.
authors.affiliation: Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, Ghent University Hospital, B-9000 Ghent, Belgium.
authors.forename: Ann Sophie
authors.initials: AS
authors.lastname: Franki
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Beneden
authors.forename: Pieter
authors.initials: P
authors.lastname: Dewint
authors.forename: Kirsten J L
authors.initials: KJ
authors.lastname: Hammond
authors.forename: Stijn
authors.initials: S
authors.lastname: Lambrecht
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000502:physiology; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000378:metabolism*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D020033:Protein Isoforms / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology
chemical_list: C505887:Ltb protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins