Analysis of Plasmacytoid and Myeloid Dendritic Cells in Nasal Epithelium

Hartmann, Evelyn; Graefe, Hendrik; Hopert, Anne; Pries, Ralph; Rothenfußer, Simon; Poeck, Hendrik; Mack, Brigitte; Endres, Stefan; Hartmann, Gunther; Wollenberg, Barbara

doi:10.1128/cvi.00172-06

Cited by 55 publications

(44 citation statements)

References 52 publications

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“…The resulting concept that mDCs and pDCs are antagonistic players, with pro-inflammatory mDC properties and tolerogenic pDC properties [29], has not yet been substantiated in humans. Recent reports demonstrate that acute upper respiratory tract infections [30] and acute allergic airway inflammation [3,31] are associated with a strong influx of pDCs into human airways. This is in keeping with the present observation that immunocompetent patients with pneumonia displayed a marked increase in airway pDC numbers.…”

Section: Discussionmentioning

confidence: 99%

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Lommatzsch¹,

Bratke²,

Bier³

et al. 2007

European Respiratory Journal

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Airway dendritic cells (DCs) are key regulators of pulmonary immune responses. However, information is limited regarding the characteristics of airway DCs in human lung diseases.Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were analysed using four-colour flow cytometry in bronchoalveolar lavage fluid (BALF) from nonsmoking controls and patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF) and pneumonia (in the presence or absence of immunosuppression).Compared with controls, immunocompetent patients with pneumonia displayed strongly enhanced pDC counts in BALF. In contrast, pDC counts in BALF from immunocompromised patients with pneumonia were even lower than in controls. This discrepancy was not explained by a different chemotactic milieu in the airways; all patients with pneumonia were characterised by strongly increased concentrations of the pDC-attracting chemokine, CXC chemokine ligand 10, in BALF. Patients with IPF were characterised by normal percentages of DC subtypes. However, the mDCs of patients with IPF were not as mature (CD83-positive) as those of controls. Patients with sarcoidosis displayed a unique increase in CD1a-negative mDCs in the airways. In addition, there was altered expression of costimulatory molecules (increased CD80 and decreased CD86 expression) on mDCs in patients with sarcoidosis.These data suggest that inflammatory diseases of the human lung are associated with a differential phenotype and recruitment of airway dendritic cells.

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Section: Discussionmentioning

confidence: 99%

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Lommatzsch¹,

Bratke²,

Bier³

et al. 2007

European Respiratory Journal

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“…Namely, although class B CpG may not be optimal for inducing the production of IFN-␣, the latter still could play a significant role by both stimulation of B cell activating factor (BAFF) (37) and activation of mDCs (38). Also, vaccine-induced CD4 ϩ T cells could play a role in the activation of mDCs through CD40-CD40L interactions (28).…”

Section: Enhancement Of Antigen Cross-presentation By Vaccine-inducedmentioning

confidence: 99%

Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming

Valmori

Souleimanian

Tosello

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

271

254

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The use of recombinant tumor antigen proteins is a realistic approach for the development of generic cancer vaccines, but the potential of this type of vaccines to induce specific CD8 ؉ T cell responses, through in vivo cross-priming, has remained unclear. In this cancer vaccine A key step in the development of generic cancer vaccines is the implementation of vaccination strategies allowing for the consistent induction of immune responses to tumor antigens. In this respect, the choice of appropriate antigens, based on both the frequency and the specificity of their expression in cancer tissues, is of paramount importance. The group of cancer/testis antigens (CTA) (1, 2), including the NY-ESO-1 antigen (3), is emerging among the most promising candidates. Because many CTA are not expressed on the surface of cancer cells but rather intracellularly, it is important that vaccination induces specific CD8 ϩ T cells able to directly recognize antigen-expressing tumor cells. Recombinant proteins can be produced in large scale and at relatively low cost, are commonly used in the development of antiviral vaccines, and are therefore attractive candidate antitumor vaccines. The potential of tumor antigen recombinant protein vaccines, however, relies on their ability not only to elicit antibody (Ab) and CD4 ϩ T cell responses but also to efficiently prime naive CD8 ϩ T cells through cross-priming (4), which generally is inefficient during spontaneous immune responses to tumor antigens (5). Professional antigen-presenting cells (APCs) detect pathogens through a variety of receptors such as the Toll-like receptors (TLR), which recognize pathogen-associated molecular patterns including CpG dinucleotides within defined flanking sequences (CpG ODN) (6). Synthetic CpG ODN able to trigger TLR9 are potent vaccine adjuvants, stimulating T helper type 1 (Th1)-type immunity (7). In humans, they can directly activate B lymphocytes and plasmacytoid dendritic cells and also indirectly activate myeloid dendritic cells (mDCs), increasing antigen cross-presentation and stimulating adaptive immune responses (8)(9)(10).In this study, we have assessed the immune response elicited by repeated vaccination with a NY-ESO-1 recombinant protein (rNY-ESO-1) administered with CpG 7909 in a water-oil emulsion with Montanide ISA-51. We show that cancer patients receiving this vaccine developed integrated Ab and CD4 ϩ T cell responses to NY-ESO-1 at an early phase of the vaccination protocol. A fraction of the patients also developed specific CD8 ϩ T cell responses at a later time point. Assessment of the correlation between the development of Ab and T cell responses suggested that the presence of sufficient levels of NY-ESO-1-specific antibodies was determinant for the cross-priming of CD8 ϩ T cells to occur in vivo. In line with this concept, we found that in vitro cross-presentation of NY-ESO-1 protein to vaccineinduced CD8 ϩ T cells by dendritic cells was enhanced by vaccine-induced Ab.

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“…During microbial infections, pDCs can accumulate in inflamed tissues such as the nasal mucosae during acute respiratory viral infections and the central nervous system during bacterial meningitis (24,25,39,53). In mice, pDCs can also infiltrate the vaginal mucosa, where they limit virus replication during acute infection such as herpes simplex virus infection (33).…”

mentioning

confidence: 99%

Characterization of Plasmacytoid Dendritic Cells in Bone Marrow of Pig-Tailed Macaques

Reeves

Fultz

2008

Clin Vaccine Immunol

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Plasmacytoid dendritic cells (pDCs), one of two types of bone marrow (BM)-derived blood DCs, play an important role in linking innate and adaptive immune responses. However, little is known about the nature of pDCs that reside in the BM. Because the simian immunodeficiency virus-macaque model closely mimics human immunodeficiency virus disease in humans, with both infections inducing a decrease in pDCs, we characterized and compared pDCs in the BM with those in peripheral blood (PB) of healthy pig-tailed macaques. The results revealed that pDCs from both compartments had the same CD123؉؉ HLA-DR ؉ Lin ؊ phenotype and were similar in size. Although BM-derived pDCs (BM-pDCs) were 3-fold greater in frequency and 10-fold greater in number, they had lower cell surface expression of both HLA-DR and the costimulatory molecule CD86 than did PB-pDCs. Both BM-and PB-pDCs responded ex vivo to synthetic CpG oligodeoxynucleotides and inactivated influenza virus by upregulating HLA-DR and CD86 and secreting cytokines; however, stimulated BM-pDCs secreted less alpha interferon and tumor necrosis factor alpha per cell than did PB-pDCs. These results suggest that while BM-pDCs appear to be phenotypically less mature than PB-pDCs, they do respond to pathogens. Thus, during acute infections, these cells could initiate immune responses either in the BM or after rapidly migrating from the BM into the periphery. A better characterization of pDCs in blood and tissues will be beneficial for future studies of macaques that focus on either pathogenesis or vaccine development.

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Analysis of Plasmacytoid and Myeloid Dendritic Cells in Nasal Epithelium

Cited by 55 publications

References 52 publications

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming

Characterization of Plasmacytoid Dendritic Cells in Bone Marrow of Pig-Tailed Macaques

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