Granzyme B is not required for regulatory T cell-mediated suppression of graft-versus-host disease.
Blood
; 115(9): 1669-77, 2010 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-19965675
ABSTRACT
Regulatory T (T(reg)) cells can suppress a wide variety of immune responses, including antitumor and alloimmune responses. The mechanisms by which T(reg) cells mediate their suppressive effects depend on the context of their activation. We previously reported that granzyme B is important for T(reg) cell-mediated suppression of antitumor immune responses. We therefore hypothesized that granzyme B may likewise be important for suppression of graft-versus-host disease (GVHD). We found that allogeneic mismatch induces the expression of granzyme B in mixed lymphocyte reactions and in a model of graft-versus-host disease (GVHD). However, wild-type and granzyme B-deficient T(reg) cells were equally able to suppress effector T (T(eff)) cell proliferation driven by multiple stimuli, including allogeneicantigen-presenting cells. Surprisingly, adoptive transfer of granzyme B-deficient T(reg) cells prevented GVHD lethality, suppressed serum cytokine production in vivo, and prevented target organ damage. These data contrast strikingly with our previous study, which demonstrated that granzyme B plays a nonredundant role in T(reg) cell-mediated suppression of antitumor responses. Taken together, these findings suggest that targeting specific T(reg) cell-suppressive mechanisms, such as granzyme B, may be therapeutically beneficial for segregating GVHD and graft-versus-tumor immune responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Granzimas
/
Doença Enxerto-Hospedeiro
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos