PLZF induces the spontaneous acquisition of memory/effector functions in T cells independently of NKT cell-related signals Journal Article

  

Authors:	Kovalovsky, D.; Alonzo, E. S.; Uche, O. U.; Eidson, M.; Nichols, K. E.; Sant'angelo, D. B.
Article Title:	PLZF induces the spontaneous acquisition of memory/effector functions in T cells independently of NKT cell-related signals
Abstract:	The broad complex, tramtrack, bric-a-brac-zinc finger (BTB-ZF) transcription factor promyelocytic leukemia zinc finger (PLZF) is required for development of the characteristic innate/effector functions of NKT cells. In this study, we report the characterization and functional analysis of transgenic mouse T cells with forced expression of PLZF. PLZF expression was sufficient to provide some memory/effector functions to T cells without the need for Ag stimulation or proliferation. The acquisition of this phenotype did not require the proliferation typically associated with T cell activation. Furthermore, PLZF transgenic cells maintained a diverse TCR repertoire, indicating that there was no preferential expansion of specific clones. Functionally, PLZF transgenic CD4 and CD8 lymphocytes were similar to wild type memory cells, in that they had similar requirements for costimulation and exhibited a similar pattern of cytokine secretion, with the notable exception that transgenic T cells produced significantly increased levels of IL-17. Whereas transgene-mediated PLZF expression was not sufficient to rescue NKT cell development in Fyn- or signaling lymphocytic activation-associated protein (SAP)-deficient mice, the acquisition of memory/effector functions induced by PLZF in conventional T cells was independent of Fyn and SAP. These data show that PLZF is sufficient to promote T cell effector functions and that PLZF acts independently of SAP- and Fyn-mediated signaling pathways. Copyright © 2010 by The American Association of Immunologists, Inc.
Keywords:	signal transduction; controlled study; unclassified drug; promoter region; genetics; nonhuman; flow cytometry; cd8+ t lymphocyte; lymphocyte proliferation; t lymphocyte; cd8-positive t-lymphocytes; mouse; phenotype; animal; cytology; metabolism; animals; mice; gene expression; cell maturation; animal experiment; transcription factor; cell differentiation; wild type; enzyme linked immunosorbent assay; mice, inbred c57bl; transgenic mouse; c57bl mouse; mice, transgenic; t lymphocyte receptor; cytokine; biosynthesis; immunology; lymphocyte activation; cytokines; signal peptide; intracellular signaling peptides and proteins; cd4+ t lymphocyte; lymphocyte clone; cd4-positive t-lymphocytes; kruppel like factor; kruppel-like transcription factors; cytokine production; effector cell; immunostimulation; interleukin 17; enzyme-linked immunosorbent assay; cytokine release; cell separation; cell expansion; t lymphocyte activation; immunologic memory; lymphocyte function; natural killer t cell; immunological memory; memory t lymphocyte; zbtb16 protein, mouse; protein kinase fyn; proto-oncogene proteins c-fyn; signaling lymphocyte activation molecule associated protein; transcription factor promyelocytic leukemia zinc finger; fyn protein, mouse; sh2d1a protein, mouse; natural killer t-cells
Journal Title:	Journal of Immunology
Volume:	184
Issue:	12
ISSN:	0022-1767
Publisher:	The American Association of Immunologists, Inc
Date Published:	2010-06-15
Start Page:	6746
End Page:	6755
Language:	English
DOI:	10.4049/jimmunol.1000776
PUBMED:	20495068
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-77953627623&partnerID=40&md5=464858fce57bc5931370929032bb7e05
Notes:	--- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: JOIMA" - "Source: Scopus"

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