Apoptosis of Peripheral T Cells in Rodent Cardiac Allograft Recipients Induced by Donor-Specific Transfusion With Impaired Inducible Costimulator/B7 Homologous Protein Allorecognition

作者：Du, J. -F.; Shen, X. -F.; Ji, X. -Q.; Chen, G.; Bai, X.; Zuo, F. -Y.; Yu, B.^*

来源：Transplantation Proceedings, 2013, 45(2): 564-568.

DOI：10.1016/j.transproceed.2012.06.084

• TRANSPLANTATION
• MECHANISMS
• TOLERANCE
• IDENTIFICATION
• REJECTION
• BLOCKADE
• PATHWAY
• ICOS

Objective. To investigate apoptosis of the CD8(+) T cells (T-c) 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(+) T-c in recipients' peripheral blood and the apoptosis of CD8(+) T-c 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 x 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(+)T(c) clone size in recipient peripheral blood (49.4% +/- 3.11% versus 50.0% +/- 2.46%, P > .05); however, the percentage of CD3(+)CD8(+)ICOS(+) T-c 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(+) T-c subpopulation in recipient draining lymph nodes was upregulated significantly at postoperative 7 days in the treatment group (19.53% +/- 5.10% versus 8.70 +/- 3.14%, P < .05).
Conclusion. Apoptosis of CD8(+) T-c 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(+) T-c subpopulation in peripheral blood and at least partially contributed to unresponsiveness toward cardiac allograft.

• 出版日期2013-3
• 单位中国人民解放军陆军总医院; 南京医科大学