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B Dendritic Cells Are Sensitized Not Anergic to Subsequent Activation1
Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia
Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II+CD86+CD40 DC, which can be generated from bone marrow in the presence of an NF-
B inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40 human monocyte-derived dendritic cells (DC), generated in the presence of an NF-
B inhibitor, signal phosphorylation of TCR
, but little proliferation or IFN-
in vitro. Proliferation is arrested in the G1/G0 phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-
production. The data indicate that signaling through NF-
B determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-
BCD40class II+ DC may either tolerize or sensitize T cells. Thus, while CD40 DC appear to "prime" or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.
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