Blood plasmacytoid dendritic cell responses to CpG oligodeoxynucleotides are impaired in human newborns

Blood ◽  
2004 ◽  
Vol 103 (3) ◽  
pp. 1030-1032 ◽  
Author(s):  
Dominique De Wit ◽  
Véronique Olislagers ◽  
Stanislas Goriely ◽  
Françoise Vermeulen ◽  
Hermann Wagner ◽  
...  
Keyword(s):  
Cord Blood ◽  
Plasmacytoid Dendritic Cell ◽  
Interferon Α ◽  
Mrna Levels ◽  
Vaccine Adjuvants ◽  
Bacterial Dna ◽  
Cpg Oligodeoxynucleotides ◽  
Cell Responses ◽  
Hla Dr ◽  
Increased Susceptibility

Abstract Plasmacytoid dendritic cells (pDCs) respond to unmethylated cytosine-phosphate-guanosine (CpG) motifs present in bacterial DNA or unmethylated synthetic oligodeoxynucleotides (CpG). In order to assess the function of pDCs in human newborns, interferon-α (IFN-α) production induced by CpG 2216 and phenotypic maturation of pDCs in response to CpG 2006 were compared in cord blood and adult blood. We first observed that neonatal pDCs displayed decreased up-regulation of CD80, CD83, CD86, and CD40, whereas HLA-DR and CD54 up-regulation did not differ significantly between adults and neonates. We then found that the production of IFN-α in response to CpG was dramatically impaired in cord blood. This neonatal defect was detected both at protein and mRNA levels and was still present in blood of 4-day-old babies. Further experiments on enriched pDCs confirmed that these cells are intrinsically deficient in CpG-induced IFN-α production at birth. These findings might be relevant to the increased susceptibility of human newborns to infections as well as to the use of CpG oligodeoxynucleotides as vaccine adjuvants in the neonatal period. (Blood. 2004;103:1030-1032)

Identification of Cord Blood Dendritic Cells as an Immature CD11c− Population

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2302-2307 ◽  
Author(s):  
Rüdiger V. Sorg ◽  
Gesine Kögler ◽  
Peter Wernet
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Graft Versus Host ◽  
Peptide Antigens ◽  
Cell Responses ◽  
Hla Dr ◽  
Lineage Markers ◽  
Low Incidence

Dendritic cells (DC) are the main stimulators of primary T-cell responses and, thus, probably play a role in the immune reactions after stem cell transplantation. Very little is known about DC in cord blood (CB) and about their potential involvement in the low incidence and severity of acute graft-versus-host disease after CB transplantation. Here, CBDC were identified as a HLA-DR+ cell population, lacking the CD3, CD11b, CD14, CD16, CD19, CD34, CD56, and glycophorin A lineage markers (lin). This lin−/HLA-DR+population represented 0.3% ± 0.1% (mean ± SD; range, 0.1% to 0.6%; n = 15) of CB mononuclear cells, and CB contained 5.4 ± 3.2 × 103 CBDC/mL (1.8 to 13.0 × 103; n = 15). CBDC expressed CD4, CD11a, CD18, CD45RA, CD50, CD54, and CD123, but showed no expression of CD1a, CD11c, CD33, CD40, CD45R0, CD80, CD83, and CD86 and only limited expression of CD58, CD102, and CD116. Despite this immature phenotype, immunomagnetically lin−-enriched CBDC were potent stimulators of allogeneic CB T cells. As few as 266 ± 107 (193 to 530; n = 10) lin−/HLA-DR+ CBDC stimulated a significant response. However, CBDC failed to take up protein or peptide antigens. Thus, in CB there is a prevalence of a DC subpopulation, resembling the CD11c− DC identified in tonsils, the so-called plasmacytoid T cells, which may exert a function distinct from the CD11c+ DC subpopulation.

Identification of Cord Blood Dendritic Cells as an Immature CD11c− Population

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2302-2307 ◽  
Author(s):  
Rüdiger V. Sorg ◽  
Gesine Kögler ◽  
Peter Wernet
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Graft Versus Host ◽  
Peptide Antigens ◽  
Cell Responses ◽  
Hla Dr ◽  
Lineage Markers ◽  
Low Incidence

Abstract Dendritic cells (DC) are the main stimulators of primary T-cell responses and, thus, probably play a role in the immune reactions after stem cell transplantation. Very little is known about DC in cord blood (CB) and about their potential involvement in the low incidence and severity of acute graft-versus-host disease after CB transplantation. Here, CBDC were identified as a HLA-DR+ cell population, lacking the CD3, CD11b, CD14, CD16, CD19, CD34, CD56, and glycophorin A lineage markers (lin). This lin−/HLA-DR+population represented 0.3% ± 0.1% (mean ± SD; range, 0.1% to 0.6%; n = 15) of CB mononuclear cells, and CB contained 5.4 ± 3.2 × 103 CBDC/mL (1.8 to 13.0 × 103; n = 15). CBDC expressed CD4, CD11a, CD18, CD45RA, CD50, CD54, and CD123, but showed no expression of CD1a, CD11c, CD33, CD40, CD45R0, CD80, CD83, and CD86 and only limited expression of CD58, CD102, and CD116. Despite this immature phenotype, immunomagnetically lin−-enriched CBDC were potent stimulators of allogeneic CB T cells. As few as 266 ± 107 (193 to 530; n = 10) lin−/HLA-DR+ CBDC stimulated a significant response. However, CBDC failed to take up protein or peptide antigens. Thus, in CB there is a prevalence of a DC subpopulation, resembling the CD11c− DC identified in tonsils, the so-called plasmacytoid T cells, which may exert a function distinct from the CD11c+ DC subpopulation.

scholarly journals Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 95
Author(s):  
Daisuke Tokuhara ◽  
Norikatsu Hikita
Keyword(s):  
Cord Blood ◽  
Protective Immunity ◽  
Current Knowledge ◽  
Current System ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Adult Humans ◽  
Neonates And Infants ◽  
Induced Immunity ◽  
Review Current

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

scholarly journals Upregulated Expression of Toll-Like Receptor 7 in Peripheral Blood Basophils of Patients With Allergic Rhinitis

2021 ◽  
pp. 194589242199303
Author(s):  
Lihong Wang ◽  
Mengmeng Zhan ◽  
Junling Wang ◽  
Dong Chen ◽  
Nan Zhao ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Mrna Levels ◽  
Toll Like Receptor ◽  
Cell Functions ◽  
Th2 Cell ◽  
Hla Dr ◽  
Ku812 Cells ◽  
Th1 Cytokine ◽  
Der P1 ◽  
Blood Granulocyte

Background Recently, it has been reported that Toll-like receptor 7 (TLR7) agonists can improve allergic rhinitis (AR) symptoms by up-regulation of Th1 cytokine release and suppression of Th2 cell functions. However, little is known of the expression of TLR7 in basophils of AR. Objective To explore the expression of TLR7 in basophils of AR, and influence of allergens on TLR7 expression. Methods The expression levels of TLR7 in basophils of patients with AR were determined by flow cytometry, and the influence of allergens on TLR7 expression was examined by real time (q) PCR. Results The percentages of TLR7+CCR3+ cells ( P < 0.001 and P = 0.011), TLR7+CD123+HLA-DR− cells ( P = 0 .016 and P = 0.042) and TLR7+CCR3+CD123+HLA-DR− cells ( P = 0.046 and P = 0.035) in blood granulocyte and mononucleated cell populations of the patients with AR were increased, respectively compared with HC subjects. TLR7 MFI on CCR3+ cells ( P = 0.050 and P = 0.043), CD123+HLA-DR− cells ( P < 0.001 and P = 0.002) and CCR3+CD123+HLA-DR− cells ( P < 0.001 and P = 0.003) were enhanced compared with HC subjects. Allergens Der p1 and OVA provoked upregulation of TLR7 expression at both protein and mRNA levels and IL-13 production in KU812 cells. House Dust Mite extract (HDME), Artemisia sieversiana wild allergen extract (ASWE), IL-31, IL-33, IL-37, and TSLP provoked elevation of IL-6 release from KU812 cells following 2 h incubation period. Conclusions The percentage of TLR7+ basophils and TLR7 expression intensity in a single basophil are both increased in the blood of patients with AR, indicating that basophils likely contribute to the pathogenesis of AR via TLR7.

scholarly journals T cell responses to a mixture of Mycobacterium tuberculosis peptides with complementary HLA-DR binding profiles

1996 ◽  
Vol 105 (3) ◽  
pp. 416-421 ◽  
Author(s):  
S. JURCEVIC ◽  
A. HILLS ◽  
G. PASVOL ◽  
R. N. DAVIDSON ◽  
J. IVANYI ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Hla Dr

scholarly journals Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Binhui Zhou ◽  
Wenyi Yang ◽  
Wushan Li ◽  
Le He ◽  
Liaoxun Lu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Plasmacytoid Dendritic Cell ◽  
White Blood Cells ◽  
Psoriatic Skin ◽  
Interferon Α ◽  
Inflammatory Disorder ◽  
Post Translational Modification ◽  
Cellular Components ◽  
Deficient Mice

Zdhhc family genes are composed of 24 members that regulate palmitoylation, a post-translational modification process for proteins. Mutations in genes that alter palmitoylation or de-palmitoylation could result in neurodegenerative diseases and inflammatory disorders. In this study, we found that Zdhhc2 was robustly induced in psoriatic skin and loss of Zdhhc2 in mice by CRISPR/Cas9 dramatically inhibited pathology of the ear skin following imiquimod treatment. As psoriasis is an inflammatory disorder, we analyzed tissue infiltrating immune cells and cytokine production. Strikingly we found that a master psoriatic cytokine interferon-α (IFN-α) in the lesioned skin of wildtype (WT) mice was 23-fold higher than that in Zdhhc2 deficient counterparts. In addition, we found that CD45+ white blood cells (WBC) infiltrating in the skin of Zdhhc2 deficient mice were also significantly reduced. Amelioration in psoriasis and dramatically reduced inflammation of Zdhhc2 deficient mice led us to analyze the cellular components that were affected by loss of Zdhhc2. We found that imiquimod induced plasmacytoid dendritic cell (pDC) accumulation in psoriatic skin, spleen, and draining lymph nodes (DLN) were drastically decreased in Zdhhc2 deficient mice, and the expression of pDC activation marker CD80 also exhibited significantly inhibited in psoriatic skin. In further experiments, we confirmed the cell intrinsic effect of Zdhhc2 on pDCs as we found that loss of zDHHC2 in human CAL-1 pDC dampened both interferon regulatory factor 7 (IRF7) phosphorylation and IFN-α production. Therefore, we identified novel function of Zdhhc2 in controlling inflammatory response in psoriasis in mice and we also confirmed that crucial role of Zdhhc2 in pDCs by regulating IRF7 activity and production of the critical cytokine. Our results finding the dependence of IFN-α production on Zdhhc2 in inflamed murine skin and in human pDCs provide rationale for targeting this new molecule in treatment of inflammation.

Sign in / Sign up

Export Citation Format

Share Document