title: Effect of cyclosporine and tacrolimus on the growth of Epstein-Barr virus-transformed B-cell lines.
abstract: BACKGROUND
  Transplant patients receiving immunosuppressive drugs are at increased risk for Epstein-Barr virus (EBV)-associated disorders including posttransplant lymphoproliferative disorder. The function of T lymphocytes, which are critical to preventing the expansion of EBV-infected B cells, is inhibited by immunosuppressive drugs. The purpose of this study was to determine whether immunosuppressive drugs have direct effects on EBV-infected B cells.
  
  
  METHODS
  The growth and proliferation of EBV-infected spontaneous lymphoblastoid cell lines (SLCLs), cultured in the presence or absence of cyclosporine (CsA) and tacrolimus (TAC), were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and [3H]thymidine incorporation assays. The effect of CsA and TAC on the viability of SLCLs was determined by cell counts with trypan blue. Apoptosis of SLCLs was induced with an anti-Fas agonist monoclonal antibody in the presence or absence of CsA and TAC and measured by flow cytometry after terminal deoxynucleotidyl transferase end-labeling and propidium iodide staining.
  
  
  RESULTS
  CsA and TAC, but not sirolimus, increased the growth of SLCLs. The increased growth in the presence of CsA and TAC was attributable to enhanced cell viability and not increased cell division of SLCLs. In addition, CsA and TAC inhibited Fas-mediated apoptosis of SLCLs.
  
  
  CONCLUSIONS
  CsA and TAC enhance the survival of EBV-transformed B-cell lines. CsA and TAC promote or augment SLCL growth through protection from cell death but do not affect cell division. The inhibition of cell death by CsA and TAC may contribute to the expansion of EBV-infected cells in immunosuppressed individuals.
authors.affiliation: Department of Surgery, Stanford University Medical Center, California 94305, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Beatty
authors.forename: S M
authors.initials: SM
authors.lastname: Krams
authors.forename: C O
authors.initials: CO
authors.lastname: Esquivel
authors.forename: O M
authors.initials: OM
authors.lastname: Martinez
mesh_terms: D001402:B-Lymphocytes / Q000473:pathology* / Q000821:virology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006566:Herpesviridae Infections / Q000473:pathology*; D004854:Herpesvirus 4, Human; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019169:Jurkat Cells; D016559:Tacrolimus / Q000494:pharmacology*; D014412:Tumor Virus Infections / Q000473:pathology*; D014775:Virus Activation / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D019014:fas Receptor; D016572:Cyclosporine; D016559:Tacrolimus