Expression and secretion of RANTES by human peripheral blood CD4+ cells are dependent on the presence of monocytes.
The cDNA for RANTES (an acronym for "Regulated upon Activation, Normal T cell Expressed and Secreted") was initially discovered by subtractive hybridization as a T cell-specific sequence. Consistent with it being a C-C (beta) chemokine, RANTES is a monocyte chemoattractant. In addition, RANTES can chemoattract unstimulated CD4+/CD45RO+ memory T cells and stimulated CD4+ and CD8+ T cells with the naive and memory phenotypes in immunologically active sites. It has been shown that CD8+ cells are dominant sources of RANTES. Here we attempted to determine if CD4+ cells express and secrete RANTES alone, or if other accessory cells (activated monocytes) are needed to activate them. We found that when autologous monocytes are added to CD4+ cells and then stimulated with phytohaemagglutinin (PHA), the quantity of RANTES, in terms of transcription and translation of the protein, is significantly higher than the amount produced by the PHA-activated monocytes alone; isolated CD4+ cells stimulated with PHA do not produce any appreciable quantity of RANTES. When CD4+ cells are primed overnight with monocytes and then stimulated with PHA, they produce more RANTES compared to PHA-stimulated CD4+ cells alone. The influence that monocytes have on CD4+ cells to produce RANTES was confirmed when the physiological activator, tumor necrosis factor-alpha (TNF-alpha), was used. These data show that CD4+ cells need monocytes to express and secrete appreciable amounts of RANTES.
Conti
P
P
Department of Oncology and Neurosciences, University of Chieti School of Medicine, Italy. pconti@unich.it
Barbacane
R C
RC
Feliciani
C
C
Reale
M
M
D015152:Blotting, Northern; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000097:blood* / Q000235:genetics*; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*
D018946:Chemokine CCL5; D012333:RNA, Messenger; D003907:Dexamethasone