title: Expression of monocyte chemoattractant protein-1 and interleukin-8 receptors on subsets of T cells: correlation with transendothelial chemotactic potential.
abstract: The differential expression of chemokine receptors may be an important mechanism for the regulation of T cell migration. To test this, we examined the expression and function of the monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8 receptors on various population of T cells. Using a simple and reliable transendothelial chemotaxis assay, both MCP-1 and IL-8 were shown to be chemotactic for subsets of blood T cells, although the relative response varied from donor to donor. To examine receptor expression and correlate it with chemotaxis of T cell subsets, monoclonal antibodies (mAb) to the receptors were produced by immunizing mice either with synthetic peptides (MCP-1 receptor), or with receptor transfectants (IL-8 receptors A and B). A flow cytometric analysis of blood T cells with an anti-MCP-1 receptor mAb revealed low expression on the CD26hi subset and undetectable expression on other T cells. Staining of T cells with anti-Il-8RA and anti-IL-8RB showed much higher levels of expression, but only on a subset of CD3+ cells which were CD8+ and CD56+. That IL-8 and MCP-1 attracted distinct subsets of T cells was best illustrated using the CD26 marker, since IL-8R+ T cells were CD26-, whereas T cells expressing detectable MCP-1R or which responded to MCP-1 in chemotaxis assays were CD26hi. T cells activated in vitro with anti-CD3 up-regulated expression of the MCP-1 receptor, but not the IL-8 receptors, and were attracted to MCP-1 much more efficiently than resting T cells. These results show that there is a clear distinction between the IL-8 and MCP-1-responsive T cell populations and that chemokine receptor expression on T cells may be regulated with respect to linkage as well as cellular activation.
authors.affiliation: LeukoSite, Inc., Cambridge, MA 02142, USA.
authors.forename: S
authors.initials: S
authors.lastname: Qin
authors.forename: G
authors.initials: G
authors.lastname: LaRosa
authors.forename: J J
authors.initials: JJ
authors.lastname: Campbell
authors.forename: H
authors.initials: H
authors.lastname: Smith-Heath
authors.forename: N
authors.initials: N
authors.lastname: Kassam
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: L
authors.initials: L
authors.lastname: Zeng
authors.forename: E C
authors.initials: EC
authors.lastname: Buthcher
authors.forename: C R
authors.initials: CR
authors.lastname: Mackay
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D001483:Base Sequence; D018932:Chemokine CCL2 / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D015846:Monokines / Q000494:pharmacology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000276:immunology; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000276:immunology; D023062:Receptors, Interleukin-8A; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A