The Journal of Experimental Medicine
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Published 16 June 2003. doi:10.1084/jem.20022234
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© Rockefeller University Press, 0022-1007/2003/6/1613 $5.00
The Journal of Experimental Medicine, Volume 197, Number 12, 1613-1621

Differential Requirement for Rel/Nuclear Factor {kappa}B Family Members in Natural Killer T Cell Development

Vallabhapurapu Sivakumar1, Kirsten J.L. Hammond2, Norma Howells1, Klaus Pfeffer3 and Falk Weih1

1 Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, 76021 Karlsruhe, Germany
2 Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
3 Institute of Medical Microbiology, Heinrich-Heine-University, 40225 Düsseldorf, Germany

Address correspondence to Falk Weih, Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, P.O. Box 3640, 76021 Karlsruhe, Germany. Phone: 49-7247-823302; Fax: 49-7247-823354; E-mail: falk.weih{at}itg.fzk.de

Natural killer T (NKT) cells have been implicated in diverse immune responses ranging from suppression of autoimmunity to tumor rejection. Thymus-dependent NKT cells are positively selected by the major histocompatibility complex class I–like molecule CD1d, but the molecular events downstream of CD1d are still poorly understood. Here, we show that distinct members of the Rel/nuclear factor (NF)-{kappa}B family of transcription factors were required in both hematopoietic and nonhematopoietic cells for normal development of thymic NKT cells. Activation of NF-{kappa}B via the classical I{kappa}B{alpha}-regulated pathway was required in a cell autonomous manner for the transition of NK-1.1–negative precursors that express the TCR V{alpha}14-J{alpha}18 chain to mature NK-1.1–positive NKT cells. The Rel/NF-{kappa}B family member RelB, on the other hand, had to be expressed in radiation resistant thymic stromal cells for the generation of early NK-1.1–negative NKT precursors. Moreover, NF-{kappa}B–inducing kinase (NIK) was required for both constitutive thymic DNA binding of RelB and the specific induction of RelB complexes in vitro. Thus, distinct Rel/NF-{kappa}B family members in hematopoietic and nonhematopoietic cells regulate NKT cell development with a unique requirement for NIK-mediated activation of RelB in thymic stroma.

Key Words: RelB • NKT cells • thymus • aly • NIK


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