| First Author | Sakoda Y | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 8 | Pages | 2506-14 |
| PubMed ID | 21220749 | Mgi Jnum | J:170521 |
| Mgi Id | MGI:4946601 | Doi | 10.1182/blood-2010-08-301325 |
| Citation | Sakoda Y, et al. (2011) Dichotomous regulation of GVHD through bidirectional functions of the BTLA-HVEM pathway. Blood 117(8):2506-14 |
| abstractText | 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. |
