Apoptosis of peripheral T cells in rodent cardiac allograft recipients induced by donor-specific transfusion with impaired inducible costimulator/B7 homologous protein allorecognition.

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). CONCLUSION: 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.