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Publication : Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo.

First Author  Yang J Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  1 Pages  147-52
PubMed ID  16373503 Mgi Jnum  J:104557
Mgi Id  MGI:3612307 Doi  10.1073/pnas.0509054103
Citation  Yang J, et al. (2006) Perforin-dependent elimination of dendritic cells regulates the expansion of antigen-specific CD8+ T cells in vivo. Proc Natl Acad Sci U S A 103(1):147-52
abstractText  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-gamma 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.
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