Allospecific rejection of MHC class I-deficient bone marrow by CD8 T cells.
Am J Transplant
; 14(1): 49-58, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24304495
ABSTRACT
Avoidance of long-term immunosuppression is a desired goal in organ transplantation. Mixed chimerism offers a promising approach to tolerance induction, and we have aimed to develop low-toxicity, nonimmunodepleting approaches to achieve this outcome. In a mouse model achieving fully MHC-mismatched allogeneic bone marrow engraftment with minimal conditioning (3 Gy total body irradiation followed by anti-CD154 and T cell-depleted allogeneic bone marrow cells), CD4 T cells in the recipient are required to promote tolerance of preexisting alloreactive recipient CD8 T cells and thereby permit chimerism induction. We now demonstrate that mice devoid of CD4 T cells and NK cells reject MHC Class I-deficient and Class I/Class II-deficient marrow in a CD8 T cell-dependent manner. This rejection is specific for donor alloantigens, since recipient hematopoiesis is not affected by donor marrow rejection and MHC Class I-deficient bone marrow that is syngeneic to the recipient is not rejected. Recipient CD8 T cells are activated and develop cytotoxicity against MHC Class I-deficient donor cells in association with rejection. These data implicate a novel CD8 T cell-dependent bone marrow rejection pathway, wherein recipient CD8 T cells indirectly activated by donor alloantigens promote direct killing, in a T cell receptor-independent manner, of Class I-deficient donor cells.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante Homólogo
/
Antígenos H-2
/
Transplante de Medula Óssea
/
Linfócitos T CD8-Positivos
/
Isoantígenos
Limite:
Animals
Idioma:
En
Revista:
Am J Transplant
Assunto da revista:
TRANSPLANTE
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Marrocos