BACKGROUND: The liver efficiently eliminates activated CD8+ T blasts. It is unknown if vaccine-primed CD8+ T blasts migrate to and establish functional CD8+ T cell immunity in the liver post-immunization. AIMS: We tested, if functional CD8+ T cell populations can be detected in the liver post-vaccination. METHODS: Murine CD8+ T cells with different epitope/restriction specificities were primed by intramuscular injection of protein- or DNA-based vaccines. The kinetics of appearance in the liver, as well as the surface phenotype and functional competence of intrahepatic, specific CD8+ T cell populations was tested. RESULTS: High numbers of specific CD8+ T cells appear in the liver after vaccination that are activated (CD69+ CD44+), express effector functions (CD27lo/CD28lo phenotype, interferon gamma secretion, specific cytolytic reactivity), but show no evidence of apoptosis (annexin V-, B220lo, similar numbers/kinetics in primed, congenic lpr/lpr mice). Specific CD8+ T cells from the liver adoptively transferred into a naïve, syngeneic host successfully reconstitute specific CD8+ T cell immunity. CONCLUSIONS: Specific, functionally competent CD8+ effector/memory T cell populations are established in the liver for months post-vaccination.
BACKGROUND: The liver efficiently eliminates activated CD8+ T blasts. It is unknown if vaccine-primed CD8+ T blasts migrate to and establish functional CD8+ T cell immunity in the liver post-immunization. AIMS: We tested, if functional CD8+ T cell populations can be detected in the liver post-vaccination. METHODS:Murine CD8+ T cells with different epitope/restriction specificities were primed by intramuscular injection of protein- or DNA-based vaccines. The kinetics of appearance in the liver, as well as the surface phenotype and functional competence of intrahepatic, specific CD8+ T cell populations was tested. RESULTS: High numbers of specific CD8+ T cells appear in the liver after vaccination that are activated (CD69+ CD44+), express effector functions (CD27lo/CD28lo phenotype, interferon gamma secretion, specific cytolytic reactivity), but show no evidence of apoptosis (annexin V-, B220lo, similar numbers/kinetics in primed, congenic lpr/lprmice). Specific CD8+ T cells from the liver adoptively transferred into a naïve, syngeneic host successfully reconstitute specific CD8+ T cell immunity. CONCLUSIONS: Specific, functionally competent CD8+ effector/memory T cell populations are established in the liver for months post-vaccination.
Authors: Nikolaus Rieber; Anna Graf; Dominik Hartl; Simon Urschel; Bernd H Belohradsky; Johannes Liese Journal: PLoS One Date: 2011-03-08 Impact factor: 3.240