title: Cyclosporin A effects during primary and secondary activation of human umbilical cord blood T lymphocytes.
abstract: OBJECTIVE
  Cyclosporin A (CsA), effective in prophylaxis and treatment of graft-vs-host disease (GVHD) after human allogeneic transplantation, blunts T-cell responses by inhibiting nuclear factor of activated T cells-1 (NFAT1) activation. This laboratory has shown that NFAT1 protein expression is severely reduced in human UCB (umbilical cord blood) T cells. Since UCB is increasingly used as a hematopoietic stem cell source in allogeneic transplantation, it is important to determine whether CsA sensitivity in UCB differs from that of adult T cells.
  
  
  METHODS
  Surface flow cytometric analysis, intracellular cytokine staining, flow cytometric analysis of cell death, and thymidine incorporation were used in this study to determine T-cell activation and effector functions during primary and secondary stimulation in the presence of CsA.
  
  
  RESULTS
  Although we observed differential CsA sensitivity of T-cell activation marker (CD69, CD45RO, CD25) upregulation comparing UCB and adult, we did not observe any significant difference in CsA sensitivity of T-cell effector functions. Importantly, we observed reduced IFN-gamma and TNF-alpha expression in UCB T cells both in primary and secondary stimulation, as well as increased rates of activation-induced cell death (AICD).
  
  
  CONCLUSIONS
  Thus, our studies do not support the previous hypothesis that reduced GVHD observed after UCB transplantation is attributable to increased CsA sensitivity of UCB T cells. Rather, reduced UCB T-cell cytokine production and increased AICD may be important cellular mechanisms underlying these favorable rates of GVHD in UCB transplant recipients.
authors: Department of Medicine, Case Western Reserve University/University Hospitals, Cleveland, OH 44106-5065, USA.
authors: S
authors: S
authors: Kadereit
authors: M M
authors: MM
authors: Kozik
authors: G R
authors: GR
authors: Junge
authors: R E
authors: RE
authors: Miller
authors: L F
authors: LF
authors: Slivka
authors: L S
authors: LS
authors: Bos
authors: K
authors: K
authors: Daum-Woods
authors: R M
authors: RM
authors: Sramkoski
authors: J W
authors: JW
authors: Jacobberger
authors: M J
authors: MJ
authors: Laughlin
mesh_terms: D000328:Adult; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D005312:Fetal Blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine