Open AccessA unique lymphotoxin αβ-dependent pathway regulates thymic emigration of Vα14 invariant natural killer T cells
Author(s) -
Ann Sophie Franki,
Katrien Van Beneden,
Pieter Dewint,
Kirsten J. L. Hammond,
Stijn Lambrecht,
Georges Leclercq,
Mitchell Kronenberg,
Dieter Deforce,
Dirk Elewaut
Publication year - 2006
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0508892103
Subject(s) - natural killer t cell , lymphotoxin , biology , microbiology and biotechnology , homing (biology) , stromal cell , lymphotoxin beta receptor , receptor , t cell , immunology , t cell receptor , immune system , cancer research , biochemistry , ecology
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.