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)-κB family of transcription factors were required in both hematopoietic and nonhematopoietic cells for normal development of thymic NKT cells. Activation of NF-κB via the classical IκBα-regulated pathway was required in a cell autonomous manner for the transition of NK-1.1–negative precursors that express the TCR Vα14-Jα18 chain to mature NK-1.1–positive NKT cells. The Rel/NF-κB 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-κB–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-κB family members in hematopoietic and nonhematopoietic cells regulate NKT cell development with a unique requirement for NIK-mediated activation of RelB in thymic stroma. RelB NKT cells thymus aly NIK Footnotes ↵ * Abbreviations used in this paper: α-GalCer, α-galactosylceramide; BM, bone marrow; DP, double positive; EMSA, electrophoretic mobility shift assay; HSA, heat-stable Ag; LT, lymphotoxin; MEF, mouse embryonic fibroblast; NF, nuclear factor; NIK, NF-κB–inducing kinase. The online version of this article contains supplemental material. Submitted: 30 December 2002 Accepted: 2 April 2003 Revision received 2 April 2003
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Differential Requirement for Rel/Nuclear Factor κB Family Members in Natural Killer T Cell Development
Sivakumar, Vallabhapurapu; Hammond, Kirsten J.L.; Howells, Norma; Pfeffer, Klaus; Weih, Falk
Follow The Journal of Experimental Medicine
, Volume 197 (12): 1613
Rockefeller University Press – Jun 16, 2003
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