The CD8 alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens
- Author(s)
- Belz, GT; Behrens, GMN; Smith, CM; Miller, JFAP; Jones, C; Lejon, K; Fathman, CG; Mueller, SN; Shortman, K; Carbone, FR; Heath, WR;
- Details
- Publication Year 2002-10-21,Volume 196,Issue #8,Page 1099-1104
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone narrow-derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8alpha(+) dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes siniplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced beta-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c(+)CD8alpha(+) cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8alpha(+) DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- RESTRICTED CROSS-PRESENTATION; IN-VIVO; T-CELLS; CD8(+); HELP; UNRESPONSIVENESS; EXPRESSION; INDUCTION; ASSAY
- Publisher's Version
- https://doi.org/10.1084/jem.20020861
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-10-21 12:00:00