Active movement of T cells away from a chemokine

Abstract

Movement towards or away from a given stimulus guides the directional migration of prokaryotes, simple eukaryotes and neurons. As bi-directional cues may influence entry and exit of immune effector cells from tissue sites, we evaluated the migratory responses of T-cell subsets to varying concentrations of the chemokine stromal cell derived factor-1 (SDF-1). There was selective repulsion of subpopulations of T cells at high concentrations of recombinant SDF-1 or naturally occurring bone marrow-derived SDF-1, which could be inhibited by pertussis toxin and antibody against the chemokine receptor CXCR4. Distinct sensitivity profiles to genistein, herbimycin and 8-Br-cAMP biochemically distinguished movement of cells towards or away from an SDF-1 gradient. In vivo, antigen-induced T-cell recruitment into the peritoneal cavity was reversed by high but not low concentrations of SDF-1. The phenomenon of movement away from a chemokine represents a previously unknown mechanism regulating the localization of mature T cells. It adds to the functional repertoire of chemokines that may participate in immune physiology and may be applied therapeutically to alter the immune response.

Tumor Necrosis Factor Blockade in Chronic Murine Tuberculosis Enhances Granulomatous Inflammation and Disorganizes Granulomas in the Lungs

“…Results of the present study using a well-established murine model of chronic tuberculosis suggest that increased inflammation and disorganization of the granuloma structure occur in the very early stage of TNF blockade therapy, when the tissue bacterial burdens are comparable among the experimental and control mouse groups. Since excessive chemokine production at the site of inflammation can result in mistrafficking of immune cells (6,32), it is possible that the enhanced inflammatory response observed in TNF-neutralized mice (a component of which is increased expression of specific chemokines) could lead to disorganization of the granulomatous structure. In the case of the B-lymphoid nodules, it is noteworthy that chemoattraction of CCR6 ϩ B lymphocytes plays a critical role in the formation of intestine-associated B-lymphoid structures (43).…”

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

“…Laboratory Investigation • May 2003 • Volume 83 • Number 5 Nagasawa et al, 1996;Poznansky et al, 2000;Sallusto et al, 1998;Voermans et al, 2001). It has been assumed that SDF-1 gene expression is constitutive in a number of tissues, because the promoter of sdf1 contains several CpG islands, a transcription factor binding motif commonly observed in housekeeping genes, and binding motifs for the transcription factors nuclear factor kappa B (NF-B) and activator protein-1 (AP-1) have not been found in a 19-kb sdf1 genomic clone (Shirozu et al, 1995).…”

“…Moreover, in the fetal liver, SDF-1 is produced by ductal plate cells, which are progenitor cells of BEC (Coulomb-L'Hermin et al, 1999). SDF-1 is not only a chemokine that is important for the development and maturation of B lineage cells but is also a chemoattractant for T cells, premature B cells, and monocytes (Bleul et al, 1996;Ma et al, 1998;Nagasawa et al, 1996;Poznansky et al, 2000;Voermans et al, 2001).…”

Plasmacytoid Dendritic Cell Recruitment by Immobilized CXCR3 Ligands

“…Fifty-microliter reaction mixtures were prepared in M lTI Ultra PCR tubes, each containing 10 mM TrisHCl, pH 8.3, 50 mM KCl, 1.5 mM MgCl 2 , 1.5 mM of each dNTP, 100 pmol primer 3Ј cxcr3 AB, 100 pmol primer 5Ј cxcr3 Aj, or 5Ј cxcr3 B, 2.5-l template, and two drops of mineral oil as top layer. After a hot start at 95°C for 5 min and addition of 1.5 U of Taq polymerase/tube, a PCR program consisting of seven touch-down cycles (denaturation at 92°C for 30 s/primer annealing at 72°C-63°C for 45 s (Ϫ1.5°C/cycle)/primer elongation at 72°C for 45 s) followed by 38 …”