T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells.
Natural killer (NK) and CD1d-restricted Valpha14i natural killer T (NKT) cells play a critical early role in host defense. Here we show that mice with a targeted deletion of T-bet, a T-box transcription factor required for Th1 cell differentiation, have a profound, stem cell-intrinsic defect in their ability to generate mature NK and Valpha14i NKT cells. Both cell types fail to complete normal terminal maturation and are present in decreased numbers in peripheral lymphoid organs of T-bet(-/-) mice. T-bet expression is regulated during NK cell differentiation by NK-activating receptors and cytokines known to control NK development and effector function. Our results identify T-bet as a key factor in the terminal maturation and peripheral homeostasis of NK and Valpha14i NKT cells.
Townsend
Michael J
MJ
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
Weinmann
Amy S
AS
Matsuda
Jennifer L
JL
Salomon
Rachelle
R
Farnham
Peggy J
PJ
Biron
Christine A
CA
Gapin
Laurent
L
Glimcher
Laurie H
LH
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018899:CpG Islands; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006706:Homeostasis; D007694:Killer Cells, Natural / Q000166:cytology / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000502:physiology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011233:Precipitin Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors