Allospecific Tregs Expanded After Anergization Remain Suppressive in Inflammatory Conditions but Lack Expression of Gut-homing Molecules.
Mol Ther
; 24(6): 1126-1134, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27049761
ABSTRACT
Cell therapy with antigen-specific regulatory T-cells (Treg) has great potential to selectively control unwanted immune responses after allogeneic stem-cell or solid organ transplantation and in autoimmune diseases. Ex vivo allostimulation with costimulatory blockade (alloanergization) of human T-cells expands populations of alloantigen-specific Treg, providing a cellular strategy to control donor T-cell alloresponses causing graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation. Crucially, it is not known if Treg expanded in this way are stable in proinflammatory conditions encountered after transplantation, or if they possess capacity to migrate to key target organs. Using an in vitro model to functionally characterize human Treg expanded after alloanergization, we now show that these cells remain potently allosuppressive in the presence of relevant exogenous inflammatory signals. Expanded allospecific Treg retained expression of molecules conferring migratory capacity to several organs but small intestine-specific chemotaxis was markedly impaired, in keeping with the preponderance of gut graft-versus-host disease in previous clinical studies using this strategy. Importantly, impaired gut-specific chemotaxis could be partially corrected by pharmacological treatment. These findings will facilitate more effective application of this cellular approach to limit T-cell alloresponses after hematopoietic stem-cell transplantation and the wider application of the strategy to other clinical settings.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Doença Enxerto-Hospedeiro
/
Isoantígenos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Reino Unido