The Transcription Factor PLZF Directs the Effector Program of the NKT Cell Lineage

The transcriptional control of CD1d-restricted NKT cell development has remained elusive. We report that PLZF (promyelocytic leukemia zinc finger, Zbtb16), a member of the BTB/POZ-ZF family of transcription factors that includes the CD4-lineage-specific c-Krox (Th-POK), is exquisitely specific to CD...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2008-09, Vol.29 (3), p.391-403
Main Authors: Savage, Adam K., Constantinides, Michael G., Han, Jin, Picard, Damien, Martin, Emmanuel, Li, Bofeng, Lantz, Olivier, Bendelac, Albert
Format: Article
Language:English
Subjects:
Animals
Antigens
Bone marrow
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cell Differentiation
Cell Lineage
Cytokines
Humans
Kinases
Kruppel-Like Transcription Factors - metabolism
Lymph Nodes - cytology
Lymph Nodes - immunology
Mice
Mice, Inbred Strains
Mice, Knockout
Mice, Transgenic
Promyelocytic Leukemia Zinc Finger Protein
Spleen - cytology
Spleen - immunology
T cell receptors
T-Lymphocytes - cytology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Thymus Gland - cytology
Thymus Gland - immunology
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Summary:The transcriptional control of CD1d-restricted NKT cell development has remained elusive. We report that PLZF (promyelocytic leukemia zinc finger, Zbtb16), a member of the BTB/POZ-ZF family of transcription factors that includes the CD4-lineage-specific c-Krox (Th-POK), is exquisitely specific to CD1d-restricted NKT cells and human MR1-specific MAIT cells. PLZF was induced immediately after positive selection of NKT cell precursors, and PLZF-deficient NKT cells failed to undergo the intrathymic expansion and effector differentiation that characterize their lineage. Instead, they preserved a naive phenotype and were directed to lymph nodes. Conversely, transgenic expression of PLZF induced CD4 + thymocytes to acquire effector differentiation and migrate to nonlymphoid tissues. We suggest that PLZF is a transcriptional signature of NKT cells that directs their innate-like effector differentiation during thymic development.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2008.07.011