Adoptive transfer of DNT cells induces long-term cardiac allograft survival and augments recipient CD4(+)Foxp3(+) Treg cell accumulation.
Transpl Immunol
; 24(2): 119-26, 2011 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-21073952
ABSTRACT
Regulatory T (Treg) cells play an important role in the regulation of immune responses but whether Treg will induce tolerance in transplant recipients in the clinic remains unknown. Our previous studies have shown that TCRαß(+)CD3(+)CD4â»CD8â»NK1.1â» (double negative, DN) T cells suppress T cell responses and prolong allograft survival in a single locus MHC-mismatched mouse model. In this study, we investigated the role of DNT cells in a more robust, fully MHC-mismatched BALB/c to C57BL/6 transplantation model, which may be more clinically relevant. Adoptive transfer of DNT cells in combination with short-term rapamycin treatment (days 1-9) induced long-term heart allograft survival (101±31 vs. 39±13 days rapamycin alone, p<0.01). Furthermore adoptive transfer DNT cells augmented CD4+Foxp3+ Treg cells accumulation in transplant recipients while depletion of CD4(+) Treg cells by anti-CD25 inhibited the effect of DNT cells on long-term graft survival (48±12 days vs. 101±31 days, p<0.001). In conclusion, DNT cells combined with short-term immunosuppression can prolong allograft survival, which may be through the accumulation of CD4(+)Foxp3(+) Treg cells in the recipient. Our result suggests that allograft tolerance may require the co-existence of different type Treg cell phenotypes which are affected by current immunosuppression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Coração
/
Linfócitos T Reguladores
/
Transferência Adotiva
/
Tolerância ao Transplante
/
Sobrevivência de Enxerto
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Transpl Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
TRANSPLANTE
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá