title: Apoptosis of peripheral T cells in rodent cardiac allograft recipients induced by donor-specific transfusion with impaired inducible costimulator/B7 homologous protein allorecognition.
abstract: OBJECTIVE
  To investigate apoptosis of the CD8(+) T cells (Tc) subpopulation in rodent cardiac allograft recipients, which were treated by donor specific transfusion combined with blockade of Inducible costimulator (ICOS)/B7 homologous protein (B7h) costimulation.
  
  
  METHODS
  Donor hearts were heterotopically transplanted into the necks of recipient mice using Chen's technique. Postoperative graft survival was recorded. Both the percentage of CD3(+)CD8(+)ICOS(+) Tc in recipients' peripheral blood and the apoptosis of CD8(+) Tc in recipient draining lymph nodes were detected by flow cytometry analysis.
  
  
  RESULTS
  In comparison with the allogeneic group, the survival of cardiac grafts was prolonged by combined treatment with 5 × 10(6) ICOS-Fc-targeted B cells on day 0 of transplantation and 10 mg/kg/d ICOS-Fc on days 0 to 6 (84.38 ± 29.14 days versus 7.00 ± 0.76 days, P < .01). The treatment group showed a stable CD8(+)Tc clone size in recipient peripheral blood (49.4% ± 3.11% versus 50.0% ± 2.46%, P > .05); however, the percentage of CD3(+)CD8(+)ICOS(+) Tc decreased significantly compared with the allogeneic group (7.5% ± 2.02% versus 14.0% ± 3.03%, P < .05). Compared with allogeneic group, apoptosis of the CD8(+) Tc subpopulation in recipient draining lymph nodes was up-regulated significantly at postoperative 7 days in the treatment group (19.53% ± 5.10% versus 8.70 ± 3.14%, P < .05).
  
  
  CONCLUSIONS
  Apoptosis of CD8(+) Tc in recipient draining lymph nodes was enhanced by pretreatment with donor specific transfusion and impaired ICOS/B7h allorecognition, which may have been associated with the variation in the CD3(+)CD8(+)ICOS(+) Tc subpopulation in peripheral blood and at least partially contributed to unresponsiveness toward cardiac allograft.
authors.affiliation: Department of General Surgery, General Hospital of Beijing Military Command, Beijing, PR China.
authors.forename: J-F
authors.initials: JF
authors.lastname: Du
authors.forename: X-F
authors.initials: XF
authors.lastname: Shen
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Ji
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Bai
authors.forename: F-Y
authors.initials: FY
authors.lastname: Zuo
authors.forename: B
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D018796:Immunoconjugates / Q000008:administration & dosage*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage*; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000378:metabolism*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000008:administration & dosage* / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D011993:Recombinant Fusion Proteins