title: Inhibition of ex vivo-expanded cytotoxic T-lymphocyte function by high-dose cyclosporine.
abstract: BACKGROUND
  Donor-derived, ex vivo-expanded cytotoxic T lymphocytes (CTL) can provide stem-cell transplantation (SCT) patients with a renewed capacity for virus-specific immune surveillance. Because SCT patients are often treated with cyclosporine (CsA), we questioned whether ex vivo-expanded CTL were susceptible to inhibition by this immunosuppressive drug.
  
  
  METHODS
  Human Epstein-Barr virus (EBV)-specific CTL were established by cultivating T cells for at least 5 weeks with interleukin (IL)-2 and irradiated, autologous EBV-transformed B-lymphoblastoid cell lines (LCL). In some cases, CsA was added during the last week of T-cell expansion. Effectors were then tested for cytotoxicity toward their targets in a chromium-release assay or by coculture with viable, unlabeled targets, in the presence or absence of CsA. Alloreactive CTL were similarly expanded and tested against major histocompatibility complex-mismatched stimulator cells.
  
  
  RESULTS
  CsA had a marginal effect on CTL function when added at concentrations greater than or equal to 250 ng/mL during the 4- to 6-hour chromium release assay. However, exposure of CTL to CsA for 1 week before assay reduced lytic function significantly. When the CTL lines were cocultured with viable targets in the presence of CsA, effectors were unable to eliminate their targets, which ultimately dominated the culture.
  
  
  CONCLUSIONS
  We suggest that the activity of ex vivo-expanded CTL may be significantly compromised in the presence of high-dose CsA in vivo, particularly if CTL are administered for the purpose of long-term virus-specific immune surveillance.
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhan
authors.forename: Brita
authors.initials: B
authors.lastname: Brown
authors.forename: Karen S
authors.initials: KS
authors.lastname: Slobod
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
mesh_terms: D016572:Cyclosporine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000502:physiology
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine