Peripheral Blood Myeloid Dendritic Cells Research Articles

Myeloid Dendritic Cells Were Expanded and Functionally Stronger in Aplastic Anemia

At present, the activated T cell-mediated destruction of hematopoietic stem/progenitor cells is the widely-recognized pathogenesis of aplastic anemia (AA). As the most important antigen-presenting cells in humans, dendritic cells (DCs) play an important role in the upstream link of immune pathogenesis in AA patients, so it may be the reason for the breakdown of immune tolerance in AA patients. In addition, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) fusion protein, can block T cell activation and function by binding CD80 and CD86 and blocking their interaction with CD28. Thus may be a potential direction for targeting DCs to treat AA. However, relevant reports have not been seen so far. To investigate the potential role of DCs in the pathogenesis of AA, we collected peripheral blood (PB) and bone marrow (BM) and measured the proportion of DCs. Results revealed that compared with healthy donors (HD), the proportion of myeloid DC in PB and BM in AA patients was significantly higher. In contrast, the proportion of plasmacytoid DC decreased significantly. Besides, the expression of CD80 and CD86 on PB DC surface of AA patients was higher than that of HD patients. Next, we cultured monocyte-derived DC in vitro and detected its phenotype and function. We confirmed that compared with HD, the expression rates of the co-stimulatory molecule CD80 and mature molecule CD83 of DC in AA patients were significantly increased, the apoptosis level was significantly decreased, and the ability to promote proliferation of CD3 +, CD4 + and CD8 + T lymphocytes was enhanced. At the same time, AA-DC significantly enhanced the ability of CD4 + T and CD8 + T cells to express CD25 and CD69. In addition, the ability of AA-DC to promote the differentiation of Th0 cells to Th1 and Th17 cells was stronger than HD. The ability to promote the differentiation of Th0 to Treg cells was weaker than HD. To investigate the feasibility of abatacept targeting DC in the treatment of AA, we compared the proportions of CTLA-4 and found the expression of CTLA-4 on CD4 + T cells and Treg cells in PB of AA patients was significantly decreased. Then, our in vitro tests confirmed that abatacept can bind to CD80 on the surface of DC and significantly down-regulate the expression of CD80. Adding abatacept into the co-culture system of DC and CD3 + T lymphocytes significantly inhibited the proliferation of CD3 +, CD4 + and CD8 + T lymphocytes, and significantly inhibited the expression of CD25 and CD69 in CD4 + T and CD8 + T cells. In addition, the ability of DC to promote the secretion of interferon-γ by CD4 + and CD8 + T cells in AA patients was significantly weakened after the addition of abatacept, while the ability to promote the secretion of interleukin-4 by CD4 + and CD8 + T cells was significantly enhanced. Finally, we performed RNA-Seq analysis using DCs cultured in vitro from HD and AA patients and using DC from AA patients added with abatacept to uncover the possible molecular mechanism. Result showed that compared with HD, there were significant differences in the expression levels of 58 genes of DC in patients with AA, including 22 up-regulated genes and 36 down-regulated genes. Go analysis inferred that the differentially expressed genes were mainly concentrated in cell migration, cell chemotaxis, regulation of cytokine production, and immune response. Besides, KEGG pathway analysis implied that the signaling pathway of significant enrichment of differentially expressed genes was cytokine-cytokine receptor interaction, NF-κB signaling pathway, chemokine signaling pathway and IL-17 signaling pathway. Meanwhile, compared with AA patients, after adding abatacept, 1058 genes showed significant differences in expression levels. Go analysis inferred that the differentially expressed genes were mainly concentrated in immune response, cytokine secretion, regulation of hemopoiesis, cell activation, differentiation, proliferation, and adhesion. Moreover, KEGG pathway analysis implied that the signaling pathway enriched in cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, NF-κB signaling pathway and Th1, Th2 and Th17 cell differentiation. Our finding revealed the increased number and hyperfunction of DC in AA patients may be involved in the immune pathogenesis of AA. Abatacept can block T cell activation by blocking the DC surface co-stimulatory molecule CD80 and is a promising strategy for AA treatment.

Metabolic surgery improves the unbalanced proportion of peripheral blood myeloid dendritic cells and T lymphocytes in obese patients.

Obesity is associated with impaired immune function and chronic low-grade inflammation. Metabolic surgery is one of the most effective therapies for treating obesity and related metabolic disorders. We aimed to explore the pathophysiological roles of peripheral dendritic cells (DCs) and T lymphocytes in metabolic surgery. In this observational cohort study, a total of 106 individuals, including obese participants with or without T2DM, overweight subjects and normal controls, were recruited. All obese participants underwent laparoscopic sleeve gastrectomy surgery and returned for the evaluation of the clinical indicators after surgery. We evaluated the frequencies of circulating DCs subsets (myeloid (mDCs) and plasmacytoid (pDCs)), the pro-inflammatory (Th1 and Th17) and anti-inflammatory (Th2 and Treg) T cell subsets by flow cytometry. Compared with normal controls, the frequencies of mDCs, Th1 and Th17 cells increased, while Treg and Th2 cells decreased in the obese participants. The frequency of mDCs and Th1 cells consistently declined after surgery compared with baseline in the obese patients and were restored to the levels observed in the normal controls after surgery. Moreover, the frequency of Treg cells was increased at 6 months after surgery in the obese patients with T2DM, and Th17 cells declined at 6 months after surgery in the severely obese patients without T2DM. This study indicates that metabolic surgery can effectively improve imbalanced immune cells in peripheral blood and restore the proportion of immune cells to a normal range during a 12-month follow-up.

Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting

BackgroundPlasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.MethodsIn this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria.ResultsWith the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria.ConclusionsThe findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

Gag-Specific CD4 T Cell Proliferation, Plasmacytoid Dendritic Cells, and Ethnicity in Perinatally HIV-1-Infected Youths: The ANRS-EP38-IMMIP Study.

In perinatally HIV-1-infected youths living in France, we previously reported that Gag-specific CD4 and CD8 T cell proliferation is more frequently detected in patients of black ethnicity than in those of other ethnicities. We observed that black patients had higher levels of dendritic cells (DCs) than other patients. We aimed at studying the association of DC levels with Gag-specific T cell proliferation. The ANRS-EP38-IMMIP study is an observational study of youths aged between 15 and 24 years who were perinatally infected with HIV. A single blood sample was drawn for virological and immunological assays. Data from cART-treated 53 youths with undetectable plasma HIV RNA were analyzed. Gag-specific T cell proliferation was assessed by using a CFSE-based test. Peripheral blood myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) were phenotyped by flow cytometry. Plasma markers were quantified by ELISA or multiplex assays. Logistic regression was used for univariate and multivariate analyses. Patients with Gag-specific CD4 T cell proliferative responses had significantly higher percentages and absolute counts of mDCs and pDCs in the peripheral blood than nonresponding patients. Gag-specific CD4 and CD8 T cell proliferation was associated with lower plasma sCD14 levels. Plasma levels of IFN-α, TRAIL, and chemokines involved in T cell migration to secondary lymphoid organs were not associated with T cell proliferation. Multivariate analysis confirmed the association between Gag-specific CD4 T cell proliferation and pDC levels. In conclusion, DC levels are a robust correlate of the presence of Gag-specific T cell proliferation in successfully treated youths.

Transient decrease in human peripheral blood myeloid dendritic cells following influenza vaccination correlates with induction of serum antibody

Dendritic cells (DC) are critical inducers of the adaptive immune response. Extensive characterization of tissue-resident and monocyte-derived DC has revealed diverse stimulatory and regulatory actions, although the role of peripheral blood dendritic cells (PBDC) in maintaining homeostasis remains unclear. Examination of various myeloid (CD11c+CD303-) and plasmacytoid (CD11c-CD303+) DC populations in the peripheral blood of seasonal trivalent inactivated influenza vaccine recipients revealed a transient decrease in the frequency of CD11c+CD1c- myeloid DC subsets 5-10 days following vaccination, including both CD141+ and CD141- myeloid DC subsets of this population. These populations rebounded by 1 month, while plasmacytoid DC remained stable. The magnitude of the decrease in the CD141+ myeloid DC subset at d5-7 significantly correlated with the induction of influenza specific serum antibodies measured at 1 month following vaccination. These results demonstrate a mobilization of peripheral blood myeloid DC following vaccination and indicate these cells are potential biomarkers of immune response.

Human Sickle Cell Disease Increases Numbers and Activation Of Peripheral Blood Myeloid Dendritic Cells, Monocytes, and Neutrophils

Sickle cell disease (SCD) is characterized by widespread vaso-occlusion in venules that is initiated by the polymerization of deoxy-hemoglobin in sickle RBCs and exacerbated by leukocyte activation and endothelial injury. In the course of the disease, episodic flare-ups result in painful vaso-occlusive crises (pVOC) and acute chest syndrome that over time result in chronic tissue injury. We have previously shown that pVOC in SCD is associated with activation of a small subset of CD1d restricted T lymphocytes known as invariant NKT (iNKT) cells that release large amounts of pro-inflammatory cytokines and propagate an inflammatory cascade. Antigen presenting cells (APCs) stimulate the activation of iNKT cells by presenting lipid antigens on CD1d and by releasing co-activating cytokines such as IL-12 and IL-18. Cytokines released by activated iNKT cells such as IFN-γ further propagate inflammation by stimulating chemotaxis of and activation of additonal leukocytes. In mice, the cytokines that are released by activated iNKT cells trans-activate monocytes and neutrophils. In this study we investigated for the first time the effect of pVOC in patients on the activation of myeloid (CD11c+/CD123-) dendritic cells (DCs) (CD45+/Lin1-/HLA-DR+), monocytes (CD3-/CD19-/CD15-/CD66b-/CD14+), and neutrophils (CD3-/CD19-/CD15+/CD66b+). Our findings indicate that like iNKT cells, myeloid DCs, monocytes, and neutrophils are increased in peripheral blood of SCD subjects relative to non-SCD controls. Plasmacytoid DCs (CD11c-/CD123+) were little affected. This increase in cell numbers is enhanced during pVOC except for myeloid DCs which decrease, possibly due to extravasation out of the blood stream. In addition, CD1d+ myeloid DCs from SCD individuals express higher levels of the activation marker, CD86, and this is further increased during pVOC. Similarly, neutrophils and monocyte subsets including classical monocytes (CD14+/CD16-) and patrolling monocytes (CD14dim/CD16+) express higher levels of activated adhesion molecules, LFA-1 (detected with KIM127 antibody) and Mac-1 (detected with CBRM1/5 antibody that recognizes active CD11b), in SCD subjects during pVOC as compared to controls and steady-state SCD patients. Taken together, these findings strongly suggest that the severity of vaso-occlusion during the clinical course of SCD correlates with an increased pro-inflammatory state reflected by increased circulating activated leukocytes. These findings are also consistent with previous murine studies showing that iNKT cells are necessary, but not sufficient for initiating and amplification of tissue inflammation and damage. The activation of CD1d+ APCs during pVOC is likely to facilitate iNKT cell activation due to the expression of co-stimulatory molecules (CD86), inflammatory cytokines, and possibly lipid antigens. Moreover, the activation of adhesion molecules on monocytes and neutrophils may enhance their propensity to contribute to vaso-occlusion. Disclosures:Field:NKT Therapeutics: Consultancy.

Increased Escherichia coli-Induced Interleukin-23 Production by CD16+Monocytes Correlates with Systemic Immune Activation in Untreated HIV-1-Infected Individuals

The level of microbial translocation from the intestine is increased in HIV-1 infection. Proinflammatory cytokine production by peripheral antigen-presenting cells in response to translocated microbes or microbial products may contribute to systemic immune activation, a hallmark of HIV-1 infection. We investigated the cytokine responses of peripheral blood myeloid dendritic cells (mDCs) and monocytes to in vitro stimulation with commensal enteric Escherichia coli in peripheral blood mononuclear cells (PBMC) from untreated HIV-1-infected subjects and from uninfected controls. Levels of interleukin 23 (IL-23) produced by PBMC from HIV-1-infected subjects in response to E. coli stimulation were significantly higher than those produced by PBMC from uninfected subjects. IL-23 was produced primarily by CD16(+) monocytes. This subset of monocytes was increased in frequency and expressed higher levels of Toll-like receptor 4 (TLR4) in HIV-1-infected individuals than in controls. Blocking TLR4 on total CD14(+) monocytes reduced IL-23 production in response to E. coli stimulation. Levels of soluble CD27, an indicator of systemic immune activation, were elevated in HIV-1-infected subjects and were associated with the percentage of CD16(+) monocytes and the induction of IL-23 by E. coli, providing a link between these parameters and systemic inflammation. Taken together, these results suggest that IL-23 produced by CD16(+) monocytes in response to microbial stimulation may contribute to systemic immune activation in HIV-1-infected individuals.

Immune Activation and Regulation in Simian Immunodeficiency Virus-Plasmodium fragile-Coinfected Rhesus Macaques

Human immunodeficiency virus (HIV) is characterized by immune activation, while chronic malaria is associated with elevated interleukin-10 (IL-10) levels. How these apparently antagonizing forces interact in the coinfected host is poorly understood. Using a rhesus macaque model of simian immunodeficiency virus (SIV)-Plasmodium fragile coinfection, we evaluated how innate immune effector cells affect the balance between immune activation and regulation. In vitro Toll-like receptor (TLR) responses of peripheral blood myeloid dendritic cells (mDC) and monocytes were temporarily associated with acute parasitemic episodes and elevated plasma IL-10 levels. Prolonged infection resulted in a decline of mDC function. Monocytes maintained TLR responsiveness but, in addition to IL-12 and tumor necrosis factor alpha, also produced IL-10. Consistent with the role of spleen in the clearance of parasite-infected red blood cells, coinfected animals also had increased splenic IL-10 mRNA levels. The main cellular source of IL-10 in the spleens of coinfected animals, however, was not splenic macrophages but T cells, suggesting an impairment of adaptive immunity. In contrast to those in spleen, IL-10-positive cells in axillary lymph nodes of coinfected animals were predominantly mDC, reminiscent of the immunosuppressive phenotype of peripheral blood mDC. Concurrent with IL-10 induction, however, SIV infection promoted elevated systemic IL-12 levels. The continuously increasing ratio of plasma IL-12 to IL-10 suggested that the overall host response in SIV-P. fragile-coinfected animals was shifted toward immune activation versus immune regulation. Therefore, SIV-P. fragile coinfection might be characterized by earlier manifestation of immune dysfunction and exhaustion than that of single-pathogen infections. This could translate into increased morbidity in HIV-malaria-coinfected individuals.

AB0202 Changes and significance of dendritic cells in peripheral blood in patients with systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by immunological intolerance, hyperactivity of various immunocyte and production of a variety of autoantibodies. Although etiology of the disease remains unclear,...

MGN-3 arabinoxylan rice bran modulates innate immunity in multiple myeloma patients.

Dendritic cells (DCs) and natural killer (NK) cells are central components of innate immunity for controlling tumor growth. The therapeutic effects of certain anti-myeloma drugs are partially mediated by targeting the innate immune response. In addition, novel types of natural compounds have been developed that efficiently modulate the activity of both the cellular and humoral compartments of immunity. MGN-3 is known as an activator of natural killer cells, inducer of apoptosis and cytokine production, and modulator of dendritic cell maturation and differentiation in vitro. We have performed a randomized, placebo-controlled study to examine the effects of MGN-3 on innate immune system parameters in 48 multiple myeloma patients. We performed immunophenotypic analysis of peripheral blood samples, determined NK cell activity, and assessed the cytokine profiles of plasma before and during 3 months of treatment. The results demonstrate a clear increase in NK activity in MGN-3-treated patients compared to the placebo group, an increased level of myeloid DCs in peripheral blood, and augmented concentrations of T helper cell type 1-related cytokines. The present study suggests that MGN-3 may represent an immunologically relevant product for activating innate immunity in multiple myeloma patients and warrants further testing to demonstrate clinical efficacy.

Dendritic cell subsets in the peritoneal fluid and peripheral blood of women suffering from ovarian cancer

Evaluation of immature myeloid and lymphoid dendritic cells (DCs) in the peritoneal fluid (PF) and peripheral blood (PB) mononuclears of women with ovarian carcinoma (n = 47) and benign ovarian tumors (n = 37). Mononuclear cells were isolated from PF and PB, stained with monoclonal antibodies (mAbs) against DC antigens (anti-BDCA-1, anti-BDCA-2), and estimated using flow cytometry. The percentage of PF myeloid DC (MDC) in mononuclears was significantly lower in patients with ovarian cancer in comparison to the group of nonmalignant ovarian tumors (0.65% and 6.95%). The percentage of PF lymphoid DCs (LDCs) was higher in patients with ovarian cancer than in the reference group (0.64% and 0.09%). The percentage of PB MDCs and LDCs did not differ significantly between studied groups. In women suffering from ovarian cancer the percentage of both MDCs and LDCs was higher in the PF than in the PB. In the reference group the percentage of MDCs was higher but that of LDCs was lower in the PF than in the PB. In women with ovarian cancer, PF MDCs/LDCs ratio was lower in comparison to patients with serous cystadenoma. In PB the ratio of MDCs to LDCs did not differ significantly between studied groups. We concluded that MDCs population may be affected by the presence of malignant disease. LDC subsets may have influence on the local immune response in the PF of women with malignant tumors of the ovary. (c) 2008 Clinical Cytometry Society.

Analysis of proteomic profiles and functional properties of human peripheral blood myeloid dendritic cells, monocyte-derived dendritic cells and the dendritic cell-like KG-1 cells reveals distinct characteristics

Important proteomic and functional differences between peripheral blood myeloid dendritic cells, monocyte-derived dendritic cells (moDC) and KG-1 cells have been identified.

Quantitative and Functional Differences between Peripheral Blood Myeloid Dendritic Cells from Patients with Pleural and Parenchymal Lung Tuberculosis

Dendritic cells (DCs) play a pivotal role in generating protective host immunity to Mycobacterium tuberculosis. Few studies have addressed DC function in the context of active tuberculosis (TB), largely due to technical constraints in obtaining adequate numbers of DC from sick patients. We quantitated peripheral blood myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the whole blood of patients with active TB and show that blood from patients with pleural TB was characterized by high circulating levels of mDCs. We also developed and optimized a novel whole-blood assay to study mDC production of the Th1-promoting cytokine interleukin 12 (IL-12) and upregulation of the maturation marker CCR7 after incubation with mycobacteria. We found that pleural TB was associated with increased IL-12 production and CCR7 expression compared to lung parenchymal disease. Our findings suggest important differences in innate immunity between patients with different forms of active TB, and this may contribute to the differences in natural history observed between the two groups.

Deficiencies in myeloid antigen‐presenting cells in women with cervical squamous intraepithelial lesions

There is little information on the function of dendritic cells in women with human papillomavirus (HPV)-related cervical squamous intraepithelial lesions (SILs). In the current study the functions of dendritic cells in the development of T-cell immunity in women with cervical SILs were assessed. The percentage of myeloid dendritic cells (MDCs) and plasmacytoid dendritic cells (PDCs) in peripheral blood were enumerated of 44 patients with SIL (low-grade, 19; high-grade, 25), 19 patients with atypical squamous cells of undetermined significance (ASCUS), and 18 controls. The expression of costimulatory receptors was assessed and the ability of monocyte-derived dendritic cells (MDDC) to present HPV16-E6 and HPV16-E7 antigens to autologous T cells. Patients with either low (L)-grade or high (H)-grade SIL had significantly lower median plasma levels of interferon-gamma than did the controls (P = .038 and .031, respectively). Compared with the controls, patients with ASCUS or LSILs had significantly lower median percentages of MDCs (P = .002 and P < .001, respectively), and significantly lower median percentages of MDDCs that expressed CD86 (P < .001 and P = .003, respectively) and major histocompatability complex class-II antigen human leukocyte antigen DR (HLA-DR) (P = .012 and P < .001, respectively). T cells of patients with ASCUS or LSILs proliferated less than those of the controls in response to HPV16-E7 (P = .002 and .046, respectively). Low levels of peripheral blood MDCs and of MDDCs expressing CD86 and HLA-DR suggest that deficiencies in the ability of MDDC to present antigen to autologous T cells may lead to persistent infection with HPV and the development of cervical SILs in HPV-infected women.

T Cell-Independent, TLR-Induced IL-12p70 Production in Primary Human Monocytes

IL-12p70 is a key cytokine for the induction of Th1 immune responses. IL-12p70 production in myeloid cells is thought to be strictly controlled by T cell help. In this work we demonstrate that primary human monocytes can produce IL-12p70 in the absence of T cell help. We show that human monocytes express TLR4 and TLR8 but lack TLR3 and TLR7 even after preincubation with type I IFN. Simultaneous stimulation of TLR4 and TLR8 induced IL-12p70 in primary human monocytes. IL-12p70 production in peripheral blood myeloid dendritic cells required combined stimulation of TLR7/8 ligands together with TLR4 or with TLR3 ligands. In the presence of T cell-derived IL-4, but not IFN-gamma, stimulation with TLR7/8 ligands was sufficient to stimulate IL-12p70 production. In monocytes, type I IFN was required but not sufficient to costimulate IL-12p70 induction by TLR8 ligation. Furthermore, TLR8 ligation inhibited LPS-induced IL-10 in monocytes, and LPS alone gained the ability to stimulate IL-12p70 in monocytes when the IL-10 receptor was blocked. Together, these results demonstrate that monocytes are licensed to synthesize IL-12p70 through type I IFN provided via the Toll/IL-1R domain-containing adaptor inducing IFN-beta pathway and the inhibition of IL-10, both provided by combined stimulation with TLR4 and TLR8 ligands, triggering a potent Th1 response before T cell help is established.

FREQUENCIES OF PERIPHERAL BLOOD MYELOID CELLS IN HEALTHY KENYAN CHILDREN WITH α+ THALASSEMIA AND THE SICKLE CELL TRAIT

The high frequencies of both alpha+ thalassemia and the sickle cell trait (hemoglobin AS [HbAS]) found in many tropical populations are thought to reflect selection pressure from Plasmodium falciparum malaria. For HbAS, but not for alpha+ thalassemia, protection appears to be mediated by the enhanced phagocytic clearance of ring-infected erythrocytes. We have investigated the genotype-specific distributions of peripheral blood leukocyte populations in two groups of children living on the coast of Kenya: a group of healthy P. falciparum parasite-negative children sampled at cross-sectional survey during a period of low malaria transmission, and a group of children attending the hospital with acute malaria. We report distinctive distributions of peripheral blood myeloid dendritic cells and monocytes in children with alpha+ thalassemia and HbAS during healthy periods and disease, and suggest ways in which these might relate to the mechanisms of protection afforded by these conditions.

Frequencies of dendritic cells (myeloid DC and plasmacytoid DC) and their ratio reduced in pregnant women: comparison with umbilical cord blood and normal healthy adults

CD11c + peripheral blood myeloid dendritic cells (MDC), and CD123 bright plasmacytoid cells (PDC), are two human dendritic cell (DC) populations. In the present study, the percentages of MDC [lin −/HLA-DR +/CD123 −/CD11c +] and PDC [lin −/HLA-DR +/CD123 bright] in a peripheral blood (PB) sample obtained from women at the time of delivery and in their umbilical cord blood (UCB) were compared with those in the PB of healthy volunteers. The percentages of MDC and PDC were determined by four-color flow cytometry. The percentages of MDC and PDC were significantly lower in the PB obtained at delivery (MDC, 0.11% ± 0.08%; PDC, 0.06% ± 0.06%) and in the UCB (MDC, 0.15% ± 0.03%; PDC, 0.05% ± 0.05%) than in the PB of the controls (males, 0.28% ± 0.12%, 0.11% ± 0.06%; females, 0.32% ± 0.13%, 0.11% ± 0.07%). Among the pregnant women at delivery, there were significant correlations between the percentage of MDC or percentage of PDC in the PB at delivery and the respective parameter in the UCB. The PB of other pregnant women, at 20–35 weeks of gestational age, also indicated significantly low percentages of MDC and PDC (0.1% ± 0.1%, 0.06% ± 0.07%). The ratio of MDC/PDC was not reduced in the UCB (4.25 ± 2.74), but was reduced in the PB obtained at delivery and the PB obtained during pregnancy (0.79 ± 0.91) in comparison with that in age-matched, nonpregnant females (3.96 ± 2.95). It was assumed that reduction of MDC during pregnancy plays an important role in maintaining immune tolerance against the embryo.

Frequencies of dendritic cells (myeloid DC and plasmacytoid DC) and their ratio reduced in pregnant women: comparison with umbilical cord blood and normal healthy adults

CD11c+ peripheral blood myeloid dendritic cells (MDC), and CD123bright plasmacytoid cells (PDC), are two human dendritic cell (DC) populations. In the present study, the percentages of MDC [lin−/HLA-DR+/CD123−/CD11c+] and PDC [lin−/HLA-DR+/CD123bright] in a peripheral blood (PB) sample obtained from women at the time of delivery and in their umbilical cord blood (UCB) were compared with those in the PB of healthy volunteers. The percentages of MDC and PDC were determined by four-color flow cytometry. The percentages of MDC and PDC were significantly lower in the PB obtained at delivery (MDC, 0.11% ± 0.08%; PDC, 0.06% ± 0.06%) and in the UCB (MDC, 0.15% ± 0.03%; PDC, 0.05% ± 0.05%) than in the PB of the controls (males, 0.28% ± 0.12%, 0.11% ± 0.06%; females, 0.32% ± 0.13%, 0.11% ± 0.07%). Among the pregnant women at delivery, there were significant correlations between the percentage of MDC or percentage of PDC in the PB at delivery and the respective parameter in the UCB. The PB of other pregnant women, at 20–35 weeks of gestational age, also indicated significantly low percentages of MDC and PDC (0.1% ± 0.1%, 0.06% ± 0.07%). The ratio of MDC/PDC was not reduced in the UCB (4.25 ± 2.74), but was reduced in the PB obtained at delivery and the PB obtained during pregnancy (0.79 ± 0.91) in comparison with that in age-matched, nonpregnant females (3.96 ± 2.95). It was assumed that reduction of MDC during pregnancy plays an important role in maintaining immune tolerance against the embryo.