Active movement of T cells away from a chemokine.
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.
Poznansky
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MC
AIDS Research Center and MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachussetts 02129, USA.
Olszak
I T
IT
Foxall
R
R
Evans
R H
RH
Luster
A D
AD
Scadden
D T
DT
D000328:Adult; D001853:Bone Marrow / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation; D037342:Pertussis Toxin; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin