scholarly journals The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

2011 ◽  
Vol 208 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Venetia Bigley ◽  
Muzlifah Haniffa ◽  
Sergei Doulatov ◽  
Xiao-Nong Wang ◽  
Rachel Dickinson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Langerhans Cells ◽  
Elevated Serum ◽  
Blood Compartment ◽  
Hla Dr ◽  
Epidermal Langerhans Cells

Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR+ lineage− compartment, with virtually no CD123+ or CD11c+ dendritic cells (DCs) and very few CD14+ or CD16+ monocytes. The only remaining HLA-DR+ lineage− cells were circulating CD34+ progenitor cells. Dermal CD14+ and CD1a+ DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR+ peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4+CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.

Expansion of CD141int Dendritic Cells in Myelodysplastic Syndrome (MDS)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3856-3856
Author(s):  
Nathalie Kerkhoff ◽  
Shahram Kordasti ◽  
Thomas Seidl ◽  
Arjan A. Van de Loosdrecht ◽  
Ghulam J. Mufti
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
High Risk ◽  
Peripheral Blood ◽  
Immune Dysregulation ◽  
Dependent Manner ◽  
Hla Dr ◽  
Healthy Donors ◽  
Exact Function

Abstract Abstract 3856 Introduction Immunological responses play an important role in the pathogenesis and progression of myelodysplastic syndromes (MDS). Several studies have confirmed that immune dysregulation in MDS may play a critical role in the initiation and progression of the dysplastic clone. We have already shown the importance of expanded Tregs in high risk MDS and its reverse correlation with the number of Th17 cells in low risk disease. However, the potential role of dendritic cells (DCs) in this immune dysregulation and in the expansion of Tregs in MDS is not fully understood. DCs are professional antigen presenting cells (APCs) and potent stimulators of T cells through (cross-)presentation of antigens via MHC class I and II molecules to CD8+ cytotoxic T lymphocytes (CTL) and CD4+ T helper (Th) cells, respectively. DCs are also important in the development of specific anti-tumor T-cell responses. Some subtypes of DCs also play an important role in the expansion of regulatory T cells (Tregs) and induce immune-suppression and editing. There are 3 main subpopulations of DCs in human: plasmacytoid DCs (CD303+ cells) and two types of myeloid DCs (CD1c+ and CD141+ cells). The aim of this study was to investigate the frequency of different DC subsets in the bone marrow and peripheral blood of MDS patients. Patients and methods Twelve peripheral blood and 26 bone marrow samples from MDS patients and 11 peripheral blood and 4 bone marrow samples from healthy donors (HDs) were studied. Three different DC subsets were investigated by flow-cytometry: plasmacytoid DC (Lineage−, HLA-DR+, CD303+), myeloid DC 1 (Lineage−, HLA-DR+, CD1c+) and myeloid DC 2 (Lineage−, HLA-DR+, CD141hi). Results Decreased frequency of DCs in peripheral blood compared to BM Frequencies of all DC subsets were significantly lower in patients' peripheral blood compared to patients' bone marrow (CD1c+ DC 2.56×102 v 7.02×102 and 0.06% v 0.33%, p=0.001; CD141+ DC 4.18×103 v 6.04×103 and 0.44% v 2.44%, p=0.005; CD303+ DC 0.06×102 v 1.07×102 and 0.01% v 0.13%, p=0.045). DC subsets The percentage of the CD1c+ DC subset was significantly reduced in the peripheral blood of MDS patients compared to HD (1.46×103 v 0.26×103, 0.18% v 0.05%, p=0.001) (figure 1). Interestingly, we have noticed an additional subset of DCs, which was not described before. The definition of this subset was based on intermediate expression of CD141 compared to previously described myeloid DCs. The CD141int subset was the only DC subset that was increased in peripheral blood of MDS patients compared to HD (0.41×102 v 2.30×102, 0.01% v 0.13%, p=0.019). Both CD1c+ and CD141int DC subsets were increased in the bone marrow of MDS patients compared to healthy donors. However, these differences were not statistically significant. Discussion Although the decreased number of circulating DCs is reported in MDS, our data suggest that this decrease is more profound in the peripheral blood compared to BM. We have also shown that this decrease is mainly in CD1c+ myeloid DCs. In this study, we describe two subsets of CD141 DCs, CD141hi and CD141int. The CD141int subpopulation is the only DC subset that is increased in MDS patients compared to HD. Our data suggest that DCs from peripheral blood may migrate to the bone marrow in response to an aberrant BM microenvironment in MDS. Nevertheless, the pattern of decrease in DC numbers is not uniform and CD141int DCs are in fact increased. It is already known that CD141+ DCs, play an important role in the induction of Tregs in an IL-10 dependent manner. We have also reported an increased number of Tregs in high-risk MDS, which correlates, with higher risk of progression toward AML. Our data suggest that CD141+ DCs may play a role in the expansion of Tregs in MDS. However, the exact function of this subset of DCs in MDS and their effect on CD4+ T-cells polarization needs to be investigated in more details. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody.

1986 ◽  
Vol 163 (4) ◽  
pp. 981-997 ◽  
Author(s):  
G Kraal ◽  
M Breel ◽  
M Janse ◽  
G Bruin
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
Precursor Cells ◽  
Peritoneal Exudate ◽  
Peritoneal Exudate Cells ◽  
Interdigitating Cells

An mAb, NLDC-145, is described that specifically reacts with a group of nonlymphoid dendritic cells including Langerhans cells (LC), veiled cells (VC), and interdigitating cells (IDC). The antibody does not react with precursor cells in bone marrow and blood. Macrophages are not stained by the antibody, but a subpopulation of Ia+ peritoneal exudate cells is recognized. Possible relationships of the various nonlymphoid dendritic cell (NLDC) types are discussed.

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

2020 ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

Abstract Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. 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, here we sought to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.Methods: In this cross-sectional study we assessed 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). Additionally, we measured plasma cytokine and chemokine levels in these adults and in Malian children (n=19) with acute symptomatic malaria.Results: With 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.Conclusions: Our findings 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 our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

scholarly journals Elevated serum levels of interleukin-5 in patients with the syndrome of episodic angioedema and eosinophilia

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 688-692 ◽  
Author(s):  
JH Butterfield ◽  
KM Leiferman ◽  
J Abrams ◽  
JE Silver ◽  
J Bower ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Important Determinant ◽  
Elevated Serum ◽  
Serum Levels ◽  
Activated T Cells ◽  
Interleukin 5 ◽  
Hla Dr ◽  
Peripheral Blood Eosinophilia ◽  
Eosinophil Degranulation

The syndrome of episodic angioedema and eosinophilia is characterized by cyclic edema, marked peripheral blood eosinophilia, and eosinophil degranulation in the dermis. Using a sensitive immunoenzymetric method, we measured serum interleukin (IL)-5 levels in four patients with this syndrome. We also determined the percentage of activated T cells in the peripheral blood of a new patient before and during an attack. In the patient presented, IL-5 levels peaked several days before maximal eosinophilia and then declined. This patient's lymphocytes showed an increased percentage, 28% (normal 2% to 3%), of activated T cells staining for both CD3 and HLA-DR 10 days before maximal eosinophilia, but no increase at the time of peak eosinophilia. In serum from three previously reported cases, elevated serum IL-5 levels were found during attacks. After glucocorticoid administration, IL-5 levels became undetectable in three of the four patients. Production of IL-5 is likely an important determinant of the pathophysiology of this syndrome.

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

2020 ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

Abstract Background: Plasmodium falciparum causes the majority of malaria cases world-wide, mostly affecting children in sub-Saharan Africa. 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, here we sought to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function.Methods: In this cross-sectional study we assessed 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). Additionally, we measured plasma cytokine and chemokine levels in these adults and in Malian children (n=19) with acute symptomatic malaria.Results: With 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.Conclusions: Our findings 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 in a manner that is comparable to mDCs of malaria-naïve individuals. 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 our understanding of asymptomatic P. falciparum infections in malaria-endemic areas.

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

2020 ◽  
Author(s):  
Triniti C. Turner ◽  
Charles Arama ◽  
Aissata Ongoiba ◽  
Safiatou Doumbo ◽  
Didier Doumtabé ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Dendritic Cell Subset ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Malaria Exposure ◽  
History Of ◽  
And Function

Abstract Background Plasmodium 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.Methods In 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.Results With 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.Conclusions The 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.

Langerhans Cell Histiocytosis: Back to Histiocytosis X

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-8-SCI-8
Author(s):  
Carl E. Allen
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
Langerhans Cell Histiocytosis ◽  
Conflicts Of Interest ◽  
Langerhans Cell ◽  
Histiocytosis X ◽  
Specific Gene ◽  
Myeloid Dendritic Cell ◽  
Epidermal Langerhans Cells

Abstract Abstract SCI-8 Langerhans cell histiocytosis (LCH) is a disorder characterized by inflammatory lesions that include pathologic CD207+ dendritic cells. LCH has pleotropic clinical presentations ranging from single lesions cured by curettage to potentially fatal multisystem disease. The first descriptions of LCH, including Hand-Schüller-Christian disease and Letterer-Siwe disease, were based on anatomic location and extent of the lesions. Despite clinical heterogeneity, LCH lesions are generally indistinguishable by histology, which led to the notion that the spectrum of clinical manifestations represents a single disorder, histiocytosis X. The designation “Langerhans cell histiocytosis” was subsequently proposed with discovery of cytoplasmic Birbeck granules in the pathologic infiltrating dendritic cells in histiocytosis X lesions, a feature shared by epidermal Langerhans cells. The etiology of LCH remains elusive, and debate of LCH as an inflammatory versus malignant disorder remains unresolved. However, recent discoveries question the model of LCH arising from transformed or pathologically activated epidermal Langerhans cells. We found cell-specific gene expression signature in CD207+ dendritic cells within LCH lesions to be more consistent with immature myeloid dendritic cell precursors than epidermal Langerhans cells. Furthermore, recent mouse studies demonstrate that CD207+ is more promiscuous than previously appreciated. Langerin (CD207) expression can be induced in many dendritic cell lineages, supporting the plausibility of a spectrum of candidates for an LCH cell of origin, including circulating dendritic cell precursors. Finally, recurrent activating BRAF mutations in LCH lesions suggest a role for a hyperactive RAS pathway in LCH pathogenesis, and possibly in normal dendritic cell development. This presentation will discuss the historical background and recent advances in LCH biology, along with a proposal to reframe “histiocytosis X” as a myeloid neoplasia caused by aberrant maturation and migration of myeloid dendritic cell precursors. Disclosures: No relevant conflicts of interest to declare.

Sézary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3287-3294 ◽  
Author(s):  
Maria Wysocka ◽  
Mohamed H. Zaki ◽  
Lars E. French ◽  
Jihed Chehimi ◽  
Michael Shapiro ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Tumor Burden ◽  
Cell Mediated Immunity ◽  
Ifn Γ ◽  
Malignant T Cells

Abstract Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma associated with involvement of the peripheral blood by malignant T cells. The disease is defined by impaired cell-mediated immunity and the production of interferon-γ (IFN-γ) and interleukin-2 (IL-2), possibly as a result of deficient IL-12 production. To understand the mechanism of this impairment, we examined the composition and function of dendritic cells and monocytes in the blood of SzS patients with different levels of peripheral blood tumor burden. Consistent with our previous observations, numbers of monocytes in SzS patients were comparable to numbers observed in healthy donors. In contrast, decreased IL-12 production correlated with a decrease in the numbers of CD11c+ dendritic cells, which was particularly profound among patients with medium (20%-50% circulating malignant T cells) and high (more than 50% circulating malignant T cells) tumor burden. Furthermore, CD123+ dendritic cells, major producers of IFN-α, were significantly diminished in SzS patients, regardless of the level of tumor burden. Granulocyte macrophage–colony-stimulating factor–treated patients experienced an increase in the number of dendritic cells but not in IFN-α or IL-12 production. However, in vitro stimulation of peripheral blood mononuclear cells from SzS patients with rCD40L and IFN-γ significantly increased the production of IL-12. Thus, our results demonstrate a profound defect in circulating dendritic cells in SzS patients that may contribute to the pathogenesis of the cytokine disorders and to the depressed cellular immunity. Importantly, the ability of rCD40L to potently induce IL-12 production from monocytes and residual dendritic cells of SzS patients could potentially serve as an immune-restorative therapeutic agent.

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