Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs

Abstract

CD8+ cytotoxic T lymphocytes (CTLs) mediate resistance to infectious agents and tumours. Classically, CTLs recognize antigens that are localized in the cytoplasm of target cells, processed and presented as peptide complexes with class I molecules of the major histocompatibility complex (MHC). However, there is evidence for an exogenous pathway whereby antigens that are not expected to gain access to the cytoplasm are presented on MHC class I molecules. The most dramatic example is the in vivo phenomenon of cross-priming: antigens from donor cells are acquired by bone-marrow-derived host antigen-presenting cells (APCs) and presented on MHC class I molecules. Two unanswered questions concern the identity of this bone-marrow-derived cell and how such antigens are acquired. Here we show that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs. Our findings suggest a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of CTLs.

Uptake of apoptotic DC converts immature DC into tolerogenic DC that induce differentiation of Foxp3+ Treg

“…Studies have shown that DC can take up antigen from dying cells and cross-present the antigenic material onto both MHC I and MHC II [20,21]. However, these studies relied on the use of mature DC to phagocytose apoptotic cells.…”

“…Surprisingly, our findings show that necrotic DC, irrespective of their maturation status are not immunostimulatory, which may be due to the paucity of the presence of certain immunosuppressive factors in primary DC, rendering them nonimmunogenic even after the cellular contents are released into the extracellular milieu. However, such factors still need to be identified.Studies have shown that DC can take up antigen from dying cells and cross-present the antigenic material onto both MHC I and MHC II [20,21]. However, these studies relied on the use of mature DC to phagocytose apoptotic cells.…”

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

“…It is well established that DCs require CD4 þ T-cell help to cross-prime CD8 þ T cells properly and this process depends on the stimulation of CD40 receptor on DCs by transiently expressed CD40L on CD4 þ T cells. 40 CD40L also provides the primary stimulus for induction of IL-12, which is critically important for generation of CTL,41 by mature DCs. [42][43][44] In vitro, CCL21 has been reported to be a chemotactic factor for CD4 þ T cells.…”

Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21WAF1/CIP1 and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity

“…Recently it has been reported that dendritic cells e ciently present antigen from apoptotic cells, stimulating class I-restricted CD8 + cytotoxic T lymphocytes (Albert et al, 1998). Phagocytic engulfment of apoptotic cells in the tumour mass should lead to enhanced antigen presentation and possibly heightened anti-tumour immune responses.…”