Cell surface CCR5 density determines the intensity of T cell migration towards rheumatoid arthritis synoviocytes.
As we have recently shown that the number of CCR5 molecules at the cell surface determines the efficiency of its function as a chemokine receptor, we tested the hypothesis that cell surface CCR5 density could influence the intensity of T lymphocyte recruitment into the rheumatoid joint. For this purpose, we established two Jurkat cell line-derived clones that differed only by their cell surface CCR5 densities. We studied their chemotaxis towards TNF-alpha-transduced rheumatoid synoviocytes supernatant. The Jurkat cell subline that expressed the higher cell surface CCR5 density migrated more intensively towards the supernatant of TNF-alpha-transduced synoviocytes than the Jurkat cell subline that expressed a lower surface CCR5 density. Moreover, this migration was blocked by an anti-CCR5 mAb. The CCR5 density on T cell surface, which is constant over time for a given individual, but varies drastically from one individual to another, might thus be a factor determining the intensity of joint inflammation in the course of RA.
Desmetz
Caroline
C
Institut de Génétique Humaine du CNRS UPR1142, Montpellier, F-34000, France.
Lin
Yea-Lih
YL
Mettling
Clément
C
Portalès
Pierre
P
Noël
Danièle
D
Clot
Jacques
J
Jorgensen
Christian
C
Corbeau
Pierre
P
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; C483024:CCL5 protein, human; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha