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Nat Immunol. 2001 Nov;2(11):1010-7.

Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells.

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1
Laboratory of Neuro-Oncology, The Rockefeller University, 1230 York Avenue, Box 26, New York, NY 10021, USA. albertm@rockvax.rockefeller.edu

Abstract

In vivo models have shown that tissue-restricted antigen may be captured by bone marrow-derived cells and cross-presented for the tolerization of CD8+ T cells. Although these studies have shown peripheral tolerization of CD8+ T cells, the mechanism of antigen transfer and the nature of the antigen-presenting cell (APC) remain undefined. We report here the establishment of an in vitro system for the study of cross-tolerance and show that dendritic cells (DCs) phagocytose apoptotic cells and tolerize antigen-specific CD8+ T cells when cognate CD4+ T helper cells are absent. Using this system, we directly tested the "two-signal" hypothesis for the regulation of priming versus tolerance. We found that the same CD83+ myeloid-derived DCs were required for both cross-priming and cross-tolerance. These data suggested that the current model for peripheral T cell tolerance, "signal 1 in the absence of signal 2", requires refinement: the critical checkpoint is not DC maturation, but instead the presence of a third signal, which is active at the DC-CD4+ T cell interface.

PMID:
11590405
DOI:
10.1038/ni722
[Indexed for MEDLINE]
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