Peripheral immunization induces functional intrahepatic hepatitis C specific immunity following selective retention of vaccine-specific CD8 T cells by the liver.
Hum Vaccin
; 7(12): 1326-35, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-22108033
ABSTRACT
It is believed that an effective HCV vaccine must induce strong HCV-specific cytotoxic IFN-γ⺠CD8⺠T cells able to migrate into and become fully activated within the liver, an organ known to suppress T cell responses and induce tolerance. Given the importance of intrahepatic HCV-specific T cells in the clearance of acute infection, the goal of this present study was to determine if peripheral immunization was able to induce functional intrahepatic HCV-specific T cell based immunity both in the presence and absence of HCV antigen expression within the liver. Using a novel HCV NS3/NS4A DNA vaccine, we show that peripheral immunization of C57BL/6 mice results in the formation of a large pool of fully functional HCV-specific cytotoxic IFN-γ⺠CD8⺠T cells within the liver and that these cells were highly enriched within the liver as compared to the spleen. Following hepatic expression of cognate HCV antigen using a previously described liver transfection method, we show that this pool of vaccine-induced HCV-specific CD8⺠T cells retained its ability to become highly activated as shown by the upregulation of IFN-γ and CCR5 expression, as well as by the clearance of HCV NS3 expressing hepatocytes. Taken together, these findings suggest that T cell effector function is preserved within the liver and that selective recruitment of antigen-specific T cells to the liver may play a previously unappreciated role in the process of immune surveillance, which may be exploited for future T cell based HCV vaccines.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatite C
/
Hepacivirus
/
Linfócitos T CD8-Positivos
/
Vacinas de DNA
/
Fígado
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Hum Vaccin
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos