In Vivo Detection of Dendritic Cell Antigen Presentation to CD4+ T Cells

Abstract

Although lymphoid dendritic cells (DC) are thought to play an essential role in T cell activation, the initial physical interaction between antigen-bearing DC and antigen-specific T cells has never been directly observed in vivo under conditions where the specificity of the responding T cells for the relevant antigen could be unambiguously assessed. We used confocal microscopy to track the in vivo location of fluorescent dye-labeled DC and naive TCR transgenic CD4+ T cells specific for an OVA peptide–I-Ad complex after adoptive transfer into syngeneic recipients. DC that were not exposed to the OVA peptide, homed to the paracortical regions of the lymph nodes but did not interact with the OVA peptide-specific T cells. In contrast, the OVA peptide-specific T cells formed large clusters around paracortical DC that were pulsed in vitro with the OVA peptide before injection. Interactions were also observed between paracortical DC of the recipient and OVA peptide-specific T cells after administration of intact OVA. Injection of OVA peptide-pulsed DC caused the specific T cells to produce IL-2 in vivo, proliferate, and differentiate into effector cells capable of causing a delayed-type hypersensitivity reaction. Surprisingly, by 48 h after injection, OVA peptide-pulsed, but not unpulsed DC disappeared from the lymph nodes of mice that contained the transferred TCR transgenic population. These results demonstrate that antigen-bearing DC directly interact with naive antigen-specific T cells within the T cell–rich regions of lymph nodes. This interaction results in T cell activation and disappearance of the DC.

Engineering of highly immunogenic long-lived DC vaccines by antiapoptotic protein gene transfer to enhance cancer vaccine potency

“…21 Finally, the endoplasmic reticulum pathway 22 is triggered by the application of various forms of stress that result in caspase activation. DC apoptosis is suggested to be induced by several pathways, such as antigen-specific T cell-induced apoptosis, which interacts with DCs, 23 or naturally occurring cell death through self-renewal machinery after completing its mission, such as antigen presentation or activation of acquired immune responses. 24 In fact, in In vivo depletion assay.…”

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

“…Both CD4 + and CD8 + T-cell-mediated killing of cognate APC populations including DCs, B cells, and macrophages has been reported in several studies [20][21][22][23][43][44][45] and was shown to be mediated via Fas ligand (FasL)-dependent 20,[46][47][48] or -independent mechanisms. 23,44 Similarly, CD8 + CTL-mediated elimination of transplanted neo-antigen-positive T cells and other hematopoietic cells has been previously demonstrated in vivo both in animal models [27][28][29] and humans.…”

“…[17][18][19] Recently, it has been documented that DCs undergo rapid apoptosis during antigen-specific interaction with T cells both in vitro 20 and in vivo. [21][22][23][24] Several studies have shown that genetically modified DCs expressing TAA could effectively process and present antigenic peptides to T cells and trigger cytotoxic response against tumor cells expressing the target antigen. 12,25 It is important to consider that the TAA-modified DCs would also become a potential target and are at risk of being eliminated by the effector T cells they have activated.…”

‘Survival gene’ Bcl-xl potentiates DNA-raised antitumor immunity

“…14 The lifespan of activated antigen-bearing DCs has been estimated to be as short as 2-3 days. 15 The longevity of new migrant DCs in the lymphoid organs is most likely key in the induction of immunity. 16,17 Thus, the efficacy of vaccines may be limited by the short-lived antigenbearing DCs in vivo.…”