Kinetics of Transcription Factors Regulating the RANTES Chemokine Gene Reveal a Developmental Switch in Nuclear Events During T-Lymphocyte Maturation

Abstract

RANTES is a chemoattractant cytokine (chemokine) whose gene is expressed immediately after stimulation of several cell types but upregulated late (3 to 5 days) after activation in normal T lymphocytes. Here we describe two cis-acting elements in the human RANTES promoter that act in T lymphocytes. One site interacts with NFIL6, which is activated within the first 24 h after T-cell activation. The second site binds an apparently novel complex that is upregulated later, between days 3 and 5. These data provide an explanation for the immediate-early expression of RANTES in some cell types and identify apparently novel factors contributing to late RANTES transcription in T cells. The results reveal a developmental switch occurring during normal T-cell maturation coincident with the onset of terminal differentiation and the binding of late-acting factors to sequences of the RANTES promoter.

JNK MAPK Pathway Regulates Constitutive Transcription of CCL5 by Human NK Cells through SP1

“…CCL5 and the cytotoxins (perforin, the granzymes, and granulysin) are up-regulated during the functional maturation of CD8 T cells 3-7 days after their initial activation by presented Ag (15)(16)(17). By contrast, NK cells display effector function when directly isolated from the peripheral blood.…”

“…In CTL, the protein is associated with the development and expression of effector function (12)(13)(14). In CD8 ϩ T cells, CCL5 transcription occurs late (3-5 days) after the activation of naive cells and is coincident with the up-regulation of perforin, the granzymes, and granulysin (15)(16)(17). A complex of nuclear proteins recruited to the promoter by Krü ppel-like factor 13 (KLF13) 3 controls the transcription of CCL5 in CTL (18,19).…”

Regulation of RANTES Chemokine Gene Expression Requires Cooperativity Between NF-κB and IFN-Regulatory Factor Transcription Factors

“…Many cell types, including fibroblasts, epithelial cells, and monocytes/macrophages, express RANTES within hours of stimulation by proinflammatory stimuli, such as TNF-␣ and IL-1␤ (13). Unlike other members of the chemokine family, which are expressed early, RANTES mRNA is induced late (3-5 days) after T cell activation (14).…”

Elevated expression of CCL5/RANTES in adult T‐cell leukemia cells: Possible transactivation of the CCL5 gene by human T‐cell leukemia virus type I tax

“…4a). 32,33,40 The A site is very important for the promoter activity since point mutations or nonsense nucleotide replacement decreases the activity by 90%. 40,41 The A site contains NF-B-like characteristics (GGAAACTCCC), especially when analyzed on the opposite DNA strand (GGGAGTTTCC), and binds both NF-B family proteins and RFLAT-1 (also named Kruppel-like factor, KLF-13 38 ).…”

“…27 31 A series of CCL5 promoter pGL2-luciferase reporter constructs described previously 32,33 were used to map Tax-responsive regions. Transient transfections were performed in Jurkat cells by electroporation using 5 ϫ 10 6 cells and 5 g of appropriate reporter and effector plasmids.…”