title: Regulation of T-lymphocyte CCL3 and CCL4 production by retinal pigment epithelial cells.
abstract: OBJECTIVE
  Retinal pigment epithelial (RPE) cells have an important role in the immune suppression associated with the immune privilege of the eye. Some aspects of this remain unclear and this study aimed to determine how RPE cells could influence the production of chemokines by T lymphocytes.
  
  
  METHODS
  T lymphocytes, separated from peripheral blood of normal volunteers, and RPE cells, cultured from donor eyes, were cultured separately and together, either in contact or in transwells. Supernatants were analyzed for CCL3, CCL4, and soluble CD54 (sCD54) by ELISA. Blocking agents were used to determine which soluble mediators were involved.
  
  
  RESULTS
  Coculture of RPE cells with activated lymphocytes resulted in a reduction in CCL3 and CCL4 production by lymphocytes, primarily by soluble mediators. Soluble CD54 was markedly increased on coculture of lymphocytes with RPE cells. Soluble CD54 reduced CCL3 and CCL4 production by RPE cells, and inhibition of CCL3 and CCL4 on coculture with RPE cells was reduced by anti-CD54. Blocking prostaglandin E2 (PGE2) abrogated the inhibition of CCL4, but not CCL3, by RPE cells. Blocking TGFβ and nitric oxide production had no effect.
  
  
  CONCLUSIONS
  RPE cells are able to down-regulate high levels of CCL3 and CCL4 production by T lymphocytes by using the soluble mediators sCD54 and PGE2. Reducing this production of CCL3 and CCL4 will dampen down the cascade effect and recruitment of more inflammatory cells, protecting the retina from an excessive immune response.
authors.affiliation: University of Aberdeen Institute of Medical Sciences, Foresterhill, Scotland, United Kingdom.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wallace
authors.forename: Gill
authors.initials: G
authors.lastname: Moir
authors.forename: David F G
authors.initials: DF
authors.lastname: Malone
authors.forename: Linda
authors.initials: L
authors.lastname: Duncan
authors.forename: Gayathri
authors.initials: G
authors.lastname: Devarajan
authors.forename: Isabel J
authors.initials: IJ
authors.lastname: Crane
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D057134:Antibodies, Neutralizing; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000378:metabolism*; D018920:Coculture Techniques; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D057134:Antibodies, Neutralizing; C515429:CCL3 protein, human; C066507:CCL4 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018799:Intercellular Adhesion Molecule-1; D015232:Dinoprostone; D007213:Indomethacin