title: Platelet factor 4 inhibits proliferation and cytokine release of activated human T cells.
abstract: Platelet factor 4 (PF-4), a platelet-derived CXC chemokine, has been shown to induce the differentiation of monocytes into a subset of macrophages that lack the expression of HLA-DR Ag. This suggests a potential role for PF-4 in the modulation of monocyte-dependent T cell activation. Using an Ag-specific stimulation model in which T cells were cocultured with monocytes in the presence of recall Ags, we could show that under these conditions PF-4-treatment caused a strong decrease of T cell proliferation as well as of IFN-gamma release. However, inhibition of T cell functions such as proliferation, IL-2 release, and IL-2 mRNA production did also occur when isolated T cells were activated in the absence of monocytes with immobilized Abs directed against CD3 in combination with cross-linked anti-CD28 Abs. The effect could be reversed when low concentrations of exogenous IL-2 instead of anti-CD28 were used as a costimulus in combination with anti-CD3 Abs. Further evidence for direct modulation of T cell function by PF-4 was obtained by the detection of specific binding sites for the chemokine on the surface of these cells. Taken together, our results show that specific binding of PF-4, resulting in the down-regulation of the IL-2-release correlates with the inhibition of functions in activated T cells.
authors.affiliation: Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fleischer
authors.forename: Evelin
authors.initials: E
authors.lastname: Grage-Griebenow
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kasper
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Martin
authors.initials: M
authors.lastname: Ernst
authors.forename: Ernst
authors.initials: E
authors.lastname: Brandt
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Flad
authors.forename: Frank
authors.initials: F
authors.lastname: Petersen
mesh_terms: D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010978:Platelet Factor 4 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; D007376:Interleukin-2; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D010978:Platelet Factor 4; D007371:Interferon-gamma