Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo
Abstract
The lifespan and survival of dendritic cells (DC) in vivo are potentially critical to the expansion of T cell immune responses. We have previously reported that DC loaded with specific antigen are rapidly eliminated by cytotoxic T lymphocytes (CTL) in vivo, but the site, mechanism, and consequences of DC elimination were not defined. In this article we show that DC elimination in vivo occurs in a perforin-dependent manner and does not require IFN-γ or the presence of CD4+CD25+ regulatory T cells. Most importantly, failure to eliminate DC had profound consequences on the CTL immune response. Perforin-deficient mice showed a progressive increase in the numbers of antigen-specific CD8+ T cells after repeated immunizations with DC. In contrast, in control mice the number of antigen-specific CD8+ T cells did not notably increase with repeated immunizations. Lastly, we also show that CTL-mediated elimination of DC occurs in peripheral tissues but not in the lymph node. Our data suggest that CTL act as "gatekeepers" that control access of antigen-loaded DC into the lymph node, thereby preventing continued expansion of antigen-specific T cells.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- January 2006
- DOI:
- 10.1073/pnas.0509054103
- Bibcode:
- 2006PNAS..103..147Y
- Keywords:
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- IMMUNOLOGY