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Transplant Proc ; 45(2): 564-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23498793

RESUMO

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.


Assuntos
Apoptose/efeitos dos fármacos , Linfócitos B/transplante , Linfócitos T CD8-Positivos/efeitos dos fármacos , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/imunologia , Imunoconjugados/administração & dosagem , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Ligante Coestimulador de Linfócitos T Induzíveis/metabolismo , Proteína Coestimuladora de Linfócitos T Induzíveis/administração & dosagem , Animais , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Citometria de Fluxo , Transplante de Coração/efeitos adversos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Recombinantes de Fusão/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
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