title: Transforming growth factor-beta/interleukin-2-induced regulatory CD4+ T cells prolong cardiac allograft survival in rats.
abstract: BACKGROUND
  Treatment of naive CD4+ T cells in vitro with transforming growth factor-beta (TGF-beta) or TGF-beta/interleukin-2 (IL-2), combined with stimulation in a mixed lymphoid culture (MLC), has been shown to generate CD4+ CD25+ regulatory T cells. However, little is known about the effect of these regulatory T cells on cardiac allograft survival in vivo.
  
  
  METHODS
  CD4+ CD25+ T cells were generated from Lewis (LEW) rat spleen through a primary MLC with TGF-beta (10 ng/ml) or TGF-beta/IL-2 (10 U/ml). The effect of adoptive transfer of the CD4+ CD25+ T cells (5.0 x 10(7)) was evaluated using an animal model of ACI rat cardiac allograft survival in LEW recipients.
  
  
  RESULTS
  The MLC with TGF-beta or TGF-beta/IL-2 generated CD4+ CD25+ regulatory T cells, which suppressed the cytotoxic activity of LEW spleen T cells against irradiated ACI spleen cells in vitro. Adoptive transfer of the CD4+ CD25+ regulatory T cells intravenously to naive syngeneic recipients significantly prolonged the ACI cardiac allograft survival (N = 6, 13.5 +/- 3.4 days) compared with the control group (N = 6, 5.0 +/- 0.6 days).
  
  
  CONCLUSIONS
  Intravenous administration of CD4+ CD25+ regulatory T cells, successfully generated by TGF-beta/IL-2 treatment, had a significant effect on cardiac allograft survival in this rat model. Adoptive transfer of regulatory T cells may represent a novel approach for preventing allograft rejection.
authors.affiliation: Department of Cardiothoracic Surgery, University of Southern California, Children's Hospital Los Angeles, Los Angeles, California 90027, USA. mbarr@surgery.usc.edu
authors.forename: Meguru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Robert L
authors.initials: RL
authors.lastname: Mencel
authors.forename: Donald V
authors.initials: DV
authors.lastname: Cramer
authors.forename: Vaughn A
authors.initials: VA
authors.lastname: Starnes
authors.forename: Mark L
authors.initials: ML
authors.lastname: Barr
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta; D014184:Transplantation, Homologous
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta