Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells.
J Immunol
; 173(8): 5008-20, 2004 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-15470044
ABSTRACT
Nonactivated CD4+CD25+ regulatory T cells constitutively express glucocorticoid-induced TNFR family-related receptor (GITR), a TNFR family member whose engagement was presumed to abrogate regulatory T cell-mediated suppression. Using GITR-/- mice, we report that GITR engagement on CD25-, not CD25+ T cells abrogates T cell-mediated suppression. Mouse APCs constitutively express GITR ligand (GITR-L), which is down-regulated following TLR signaling in vivo. Although GITR-/-CD25- T cells were capable of mounting proliferative responses, they were incapable of proliferation in the presence of physiological numbers of CD25+ T cells. Thus, GITR-L provides an important signal for CD25- T cells, rendering them resistant to CD25+ -mediated regulation at the initiation of the immune response. The down-regulation of GITR-L by inflammatory stimuli may enhance the susceptibility of effector T cells to suppressor activity during the course of an infectious insult.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Interleucina-2
/
Proteínas de Transporte
/
Antígenos CD4
/
Receptores de Fator de Crescimento Neural
/
Linfócitos T Reguladores
/
Receptores do Fator de Necrose Tumoral
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article