The Acquisition of Antigen Cross-Presentation Function by Newly Formed Dendritic Cells

Sathe, Priyanka; Pooley, Joanne; Vremec, David; Mintern, Justine D.; Jin, Jun‐O; Wu, Li; Kwak, Jong‐Young; Villadangos, José A; Shortman, Ken

doi:10.4049/jimmunol.1002683

Cited by 99 publications

(130 citation statements)

References 35 publications

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“…6B), indicating that at least in the thymus, CD103 is not directly associated with cross-presentation. Interestingly, it was shown in a parallel study with DCs produced in Flt3 ligand-stimulated BM cultures, that acquisition of crosspresentation capacity is promoted by GM-CSF, and that although this coincided with expression of CD103, the expression of this molecule was dissociated from the capacity to cross-present [29]. Taken together, these results indicate that, as opposed to splenic CD8…”

Section: Cd103mentioning

confidence: 78%

“…Accordingly, it has been recently shown in two independent studies that splenic CD8 1 DCs are heterogeneous regarding their ability to cross-present antigens [11,12]. Since IL-3, TGFb, and GM-CSF promote CD103 expression [29], variability of these cytokines could be the source of the differences concerning CD103 expression/cross-presentation by splenic DCs from different laboratories. Furthermore, GM-CSF is commonly added to in vitro cross-presentation assays, incorrectly leading to the conclusion that splenic CD8 1 DCs are intrinsically capable of antigen cross-presentation.…”

Section: Licensing the Defect Of Splenic Cd8mentioning

confidence: 99%

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Thymic but not splenic CD8⁺ DCs can efficiently cross‐prime T cells in the absence of licensing factors

et al. 2011

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Cross-presentation is an important mechanism to elicit both immune defenses and tolerance. Although only a few DC subsets possess the machinery required for crosspresentation, little is known about differences in cross-presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. In this study, we demonstrate that steady-state thymic CD81 DCs can efficiently cross-prime naïve CD8 1 T cells in the absence of costimulation. Surprisingly, cross-priming by splenic CD8 1 DCs was dependent on licensing factors such as GM-CSF. In the absence of GM-CSF,antigen-MHC-class-I complexes were detected on thymic but not on splenic CD8 1 DCs, indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences between thymic and splenic CD8 1 DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. Moreover, we did not detect overall impairment of antigen presentation, as peptide-loaded splenic CD8 1 DCs were able to induce CD8 1 T-cell proliferation. The observation that thymic CD8 1 DCs are more efficient than splenic CD8 1 DCs in T-cell cross-priming in the absence of licensing factors indicates that the requirements for efficient antigen presentation differ between these cells.

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Section: Cd103mentioning

confidence: 78%

Section: Licensing the Defect Of Splenic Cd8mentioning

confidence: 99%

Thymic but not splenic CD8⁺ DCs can efficiently cross‐prime T cells in the absence of licensing factors

et al. 2011

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“…Bone marrow-derived BALB/c dendritic cells were obtained as described. 27 Infection of cells with rVACV was performed at a m.o.i. of 3-15 as described.…”

Section: Cell Lines and Virus Infectionmentioning

confidence: 99%

Exogenous, TAP‐independent lysosomal presentation of a respiratory syncytial virus CTL epitope

et al. 2012

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Respiratory syncytial virus causes lower respiratory tract infections in infancy and old age, affecting also immunocompromised patients. The viral fusion protein is an important vaccine candidate eliciting antibody and cell-mediated immune responses. CD8 þ cytotoxic T lymphocytes (CTLs) are known to have a role in both lung pathology and viral clearance. In BALB/c mice, the fusion protein epitope F249-258 is presented to CTLs by the murine major histocompatibility complex (MHC) class I molecule K d . In cells infected with recombinant vaccinia viruses encoding the fusion protein, F249-258 is presented by MHC class I molecules through pathways that are independent of the transporters associated with antigen processing (TAP). We have now found that F249-258 can be generated from non-infectious virus from an exogenous source. Antigen processing follows a lysosomal pathway that appears to require autophagy. As a practical consequence, inactivated virus suffices for in vivo priming of virus-specific CTLs. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants and young children, 3 affecting also immunocompromised patients and the elderly. The fusion (F) glycoprotein of RSV is a major vaccine candidate as it is an important target for neutralising antibodies 4 and virus-specific CTLs. 5 Studies in the mouse model of human RSV have shown that CTLs have a role both in lung pathology and viral clearance. 6,7 In previous studies,

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“…This established culture system has enabled detailed studies of the specialized function and development of murine DC subsets. [8][9][10][11] The study of human DC has lagged behind. Initial studies on human DC have focused on DC found in blood.…”

Section: Introductionmentioning

confidence: 99%

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

et al. 2012

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Dendritic cells (DCs) are immune cells specialized to capture, process and present antigen to T cells in order to initiate an appropriate adaptive immune response. The study of mouse DC has revealed a heterogeneous population of cells that differ in their development, surface phenotype and function. The study of human blood and spleen has shown the presence of two subsets of conventional DC including the CD1b/c 1 and CD141 1 CLEC9A 1 conventional DC (cDC) and a plasmacytoid DC (pDC) that is CD304 1 CD123 1 . Studies on these subpopulations have revealed phenotypic and functional differences that are similar to those described in the mouse. In this study, the three DC subsets have been generated in vitro from human CD34 1 precursors in the presence of fms-like tyrosine kinase 3 ligand (Flt3L) and thrombopoietin (TPO). The DC subsets so generated, including the CD1b/c 1 and CLEC9A 1 cDCs and CD123 1 pDCs, were largely similar to their blood and spleen counterparts with respect to surface phenotype, toll-like receptor and transcription factor expression, capacity to stimulate T cells, cytokine secretion and cross-presentation of antigens. This system may be utilized to study aspects of DC development and function not possible in vivo.

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The Acquisition of Antigen Cross-Presentation Function by Newly Formed Dendritic Cells

Cited by 99 publications

References 35 publications

Thymic but not splenic CD8⁺ DCs can efficiently cross‐prime T cells in the absence of licensing factors

Thymic but not splenic CD8⁺ DCs can efficiently cross‐prime T cells in the absence of licensing factors

Exogenous, TAP‐independent lysosomal presentation of a respiratory syncytial virus CTL epitope

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

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The Acquisition of Antigen Cross-Presentation Function by Newly Formed Dendritic Cells

Cited by 99 publications

References 35 publications

Thymic but not splenic CD8+ DCs can efficiently cross‐prime T cells in the absence of licensing factors

Thymic but not splenic CD8+ DCs can efficiently cross‐prime T cells in the absence of licensing factors

Exogenous, TAP‐independent lysosomal presentation of a respiratory syncytial virus CTL epitope

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

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Thymic but not splenic CD8⁺ DCs can efficiently cross‐prime T cells in the absence of licensing factors

Thymic but not splenic CD8⁺ DCs can efficiently cross‐prime T cells in the absence of licensing factors