Dichotomous regulation of GVHD through bidirectional functions of the BTLA-HVEM pathway.
Blood
; 117(8): 2506-14, 2011 Feb 24.
Article
em En
| MEDLINE
| ID: mdl-21220749
ABSTRACT
B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor that interacts with herpesvirus entry mediator (HVEM), and this interaction regulates pathogenesis in various immunologic diseases. In graft-versus-host disease (GVHD), BTLA unexpectedly mediates positive effects on donor T-cell survival, whereas immunologic mechanisms of this function have yet to be explored. In this study, we elucidated a role of BTLA in GVHD by applying the newly established agonistic anti-BTLA monoclonal antibody that stimulates BTLA signal without antagonizing BTLA-HVEM interaction. Our results revealed that provision of BTLA signal inhibited donor antihost T-cell responses and ameliorated GVHD with a successful engraftment of donor hematopoietic cells. These effects were dependent on BTLA signal into donor T cells but neither donor non-T cells nor recipient cells. On the other hand, expression of BTLA mutant lacking an intracellular signaling domain restored impaired survival of BTLA-deficient T cells, suggesting that BTLA also serves as a ligand that delivers HVEM prosurvival signal in donor T cells. Collectively, current study elucidated dichotomous functions of BTLA in GVHD to serve as a costimulatory ligand of HVEM and to transmit inhibitory signal as a receptor.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
/
Transdução de Sinais
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Membro 14 de Receptores do Fator de Necrose Tumoral
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Doença Enxerto-Hospedeiro
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2011
Tipo de documento:
Article