The functional immaturity of dendritic cells can be relevant to increased tolerance associated with cord blood transplantation

Encabo, Araceli; Solves, Pilar; Carbonell-Uberos, Francisco; Miñana, María‐Dolores

doi:10.1111/j.1537-2995.2007.01103.x

Cited by 41 publications

(40 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, although CpG and R-848 molecules have been shown to display promising adjuvant activities in adults [26,27], the use of these TLR agonists as neonatal vaccine adjuvants needs to be revisited in light of the present findings. Finally, defective IRF-7/type I IFN axis in cord blood pDC could also have important implications for the understanding of higher susceptibility to microbial infections encountered after cord blood cell transplantation [28,29]. After viral exposure, cell samples were stained as described in Materials and methods and run on the ImageStream machine.…”

Section: Discussionmentioning

confidence: 99%

Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

et al. 2008

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDC) are specialized in massive production of type I interferons (IFN) upon viral infections. Activation of IFN regulatory factor (IRF)-7 is critically required for the synthesis of type I IFN in pDC. IRF-7 is highly expressed by resting pDC and translocates into the nucleus to initiate type I IFN transcription. In a previous work, we observed an impaired IFN-a production in enriched cord blood pDC following a TLR9 stimulation using CpG oligonucleotides. Herein, we show that highly purified pDC from cord blood exhibit a profound defect in their capacity to produce IFN-a/b in response to TLR9 as well as to TLR7 ligation or human CMV or HSV-1 exposure. Microarray experiments indicate that expression of the majority of type I IFN subtypes induced by a TLR7 agonist is reduced in cord blood pDC. We next demonstrated a reduced nuclear translocation of IRF-7 in cord blood pDC following CpG and HSV stimulation as compared to adult pDC. We conclude that impaired IRF-7 translocation in cord blood pDC is associated with defective expression of type I IFN genes. Our data provide a molecular understanding for the decreased ability of cord blood pDC to produce type I IFN upon viral stimulation.

show abstract

Section: Discussionmentioning

confidence: 99%

Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Then, depending on the type of initial maturation signals, they polarize the resulting adaptive immune response [11]. Neonatal DCs display defective expression of co-stimulatory molecules [10,[12][13][14][15][16] and a deficient production of the type 1 polarizing cytokines interleukin (IL)-12 and IFN-b [17,18]. They are less effective than adult DCs in stimulating T cell proliferation [19,20] and induce a poor Th1 response [21,22].…”

Section: Introductionmentioning

confidence: 99%

Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

Rodríguez

Carlier

Truyens

2011

Med Microbiol Immunol

View full text Add to dashboard Cite

We previously reported that Trypanosoma cruzi, the agent of Chagas disease, induces in congenitally infected fetuses a strong, adult-like parasite-specific CD8(+) T cell response producing IFN-γ (Hermann et al. in Blood 100:2153-2158, 2002). This suggests that the parasite is able to overcome the immaturity of neonatal antigen presenting cells, an issue which has not been previously addressed. We therefore investigated in vitro the ability of T. cruzi to activate cord blood DCs and compared its effect to that on adult cells. We show that T. cruzi induces phenotypic maturation of cord blood CD11c(+) myeloid DCs (mDCs), by enhancing surface expression of CD40, CD80, and CD83, and that parasite-specific IgG purified from cord blood of neonates born to T. cruzi-infected mothers amplify such expression. CD83, considered as the best marker of mature DCs, reaches higher level on cord blood than on adult mDCs. Allo-stimulation experiments showed that T. cruzi-activated cord blood mononuclear cells enriched in DCs (eDCs) stimulate proliferation of cord blood and adult CD3(+) T cells to a similar extent. Of note, T. cruzi-activated eDCs from cord blood trigger more potent proliferation of CD8(+) than CD8(-) (mainly CD4(+)) adult T cells, a feature not observed with adult eDCs. T cell proliferation is associated with IFN-γ release and down-regulation of IL-13 production. These data show that T. cruzi potently activates human cord blood mDCs and endows eDCs to trigger CD8(+) T cell proliferation and favor type 1 immune response. Interestingly, maternal antibodies can strengthen the development of mature DCs that might contribute to overcome the immunological immaturity associated with early life.

show abstract

“…In contrast, when CpG-C274 or influenza virus was added at the time that the BMMC and PBMC cultures were established, the secretion of both cytokines was upregulated, and regardless of the stimulus, there was no statistically significant difference in the amount of either IFN-␣ or TNF-␣ that accumulated in the medium. Encabo et al (20) recently reported that DCs from umbilical cord blood were phenotypically less mature and secreted less TNF-␣ than PB-DCs. This difference might be true for pDCs in the BM, consistent with the more immature phenotype of these cells.…”

Section: Vol 15 2008 Bone Marrow Plasmacytoid Dendritic Cells In Mamentioning

confidence: 99%

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

Reeves

Fultz

2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

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.

show abstract

The functional immaturity of dendritic cells can be relevant to increased tolerance associated with cord blood transplantation

Abstract: The tolerogenic immunophenotype and diminished functionality of CB DCs can be important to create a microenvironment where Treg develop, that in turn may be relevant to observed lower incidence of chronic GVHD after CB transplantation.

Cited by 41 publications

References 35 publications

Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

Interferon regulatory factor 7‐mediated responses are defective in cord blood plasmacytoid dendritic cells

Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

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

Contact Info

Product

Resources

About