Regulating mammalian target of rapamycin to tune vaccination-induced CD8(+) T cell responses for tumor immunity.
J Immunol
; 188(7): 3080-7, 2012 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-22379028
ABSTRACT
Vaccine strategies aimed at generating CD8(+) T cell memory responses are likely to show augmented efficacy against chronic challenges like tumor. The abundance in variety of memory CD8(+) T cells behooves development of vaccine strategies that generate distinct memory responses and evaluate them for tumor efficacy. In this study, we demonstrate the ability of a variety of rapamycin treatment regimens to regulate virus vaccination-induced CD8(+) T cell memory responses and tumor efficacy. Strikingly, a short course of high-dose, but not low-dose, rapamycin treatment transiently blocks viral vaccination-induced mammalian target of rapamycin activity in CD8(+) T cells favoring persistence and Ag-recall responses over type 1 effector maturation; however, prolonged high-dose rapamycin administration abrogated memory responses. Furthermore, a short course of high-dose rapamycin treatment generated CD8(+) T cell memory responses that were independent of IL-15 and IL-7 and were programmed early for sustenance and greater tumor efficacy. These results demonstrate the impact a regimen of rapamycin treatment has on vaccine-induced CD8(+) T cell responses and indicates that judicious application of rapamycin can augment vaccine efficacy for chronic challenges.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timoma
/
Neoplasias do Timo
/
Proteínas
/
Adjuvantes Imunológicos
/
Vacinação
/
Linfócitos T CD8-Positivos
/
Vacinas Anticâncer
/
Sirolimo
/
Memória Imunológica
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article