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Full-Text Articles in Medical Sciences

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill Jun 2017

Impact Of The C-Mybe308g Mutation On Mouse Myelopoiesis And Dendritic Cell Development, Peter Papathanasiou, Sawang Petvises, Ying-Ying Hey, Andrew C Perkins, Helen C O'Neill

Helen O'Neill

Booreana mice carrying the c-Myb308G point mutation were analyzed to determine changes in early hematopoiesis in the bone marrow and among mature cells in the periphery. This point mutation led to increased numbers of early hematopoietic stem and progenitor cells (HSPCs), with a subsequent reduction in the development of B cells, erythroid cells, and neutrophils, and increased numbers of myeloid cells and granulocytes. Myelopoiesis was further investigated by way of particular subsets affected. A specific question addressed whether booreana mice contained increased numbers of dendritic-like cells (L-DC subset) recently identified in the spleen, since L-DCs arise in vitro by direct …


Redefining Myeloid Subsets In Murine Spleen, Ying-Ying Hey, Jonathan K H Tan, Helen C O'Neill Oct 2016

Redefining Myeloid Subsets In Murine Spleen, Ying-Ying Hey, Jonathan K H Tan, Helen C O'Neill

Helen O'Neill

Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed "L-DC" in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11b(hi)CD11c(lo)MHCII(-)Ly6C(-)Ly6G(-) subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level …


The B Subunit Of Escherichia Coli Heat-Labile Toxin Alters The Development And Antigen-Presenting Capacity Of Dendritic Cells, Jing Ji, Kristin Grifftiths, Peter Milburn, Timothy Hirst, Helen O'Neill Aug 2015

The B Subunit Of Escherichia Coli Heat-Labile Toxin Alters The Development And Antigen-Presenting Capacity Of Dendritic Cells, Jing Ji, Kristin Grifftiths, Peter Milburn, Timothy Hirst, Helen O'Neill

Helen O'Neill

Escherichia coli's heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and myeloid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of …


Etxb Alters The Activation State Of Mature Dendritic Cell Subsets, J Ji, Kristin Griffiths, P Milburn, T Hirst, Helen O'Neill Dec 2014

Etxb Alters The Activation State Of Mature Dendritic Cell Subsets, J Ji, Kristin Griffiths, P Milburn, T Hirst, Helen O'Neill

Helen O'Neill

No abstract provided.


Expression Of Tcr-Vbeta Peptides By Murine Bone Marrow Cells Does Not Identify T Cell Progenitors, Janice Abbey, Holger Karunsky, Thomas Serwold, Peter Papathanasiou, Irving Weissman, Helen O'Neill Dec 2014

Expression Of Tcr-Vbeta Peptides By Murine Bone Marrow Cells Does Not Identify T Cell Progenitors, Janice Abbey, Holger Karunsky, Thomas Serwold, Peter Papathanasiou, Irving Weissman, Helen O'Neill

Helen O'Neill

Germline transcription has been described for both immunoglobulin and T-cell receptor (TCR) genes, raising questions of their functional significance during haematopoiesis. Previously, an immature murine T-cell line was shown to bind antibody to TCR-Vβ8.2 in absence of anti-Cβ antibody binding, and an equivalent cell subset was also identified in the mesenteric lymph node. Here, we investigate whether germline transcription and cell surface Vβ8.2 expression could therefore represent a potential marker of T-cell progenitors. Cells with the TCR phenotype of Vβ8.2+Cβ- are found in several lymphoid sites, and among the lineage-negative (Lin-) fraction of hematopoietic progenitors in bone marrow (BM). Cell …


Delineation Of A Novel Dendritic-Like Subset In Human Spleen., Sawang Petvises, D Talaulikar, Helen O'Neill Dec 2014

Delineation Of A Novel Dendritic-Like Subset In Human Spleen., Sawang Petvises, D Talaulikar, Helen O'Neill

Helen O'Neill

No abstract provided.


Characterisation Of Dendritic Cells Arising From Progenitors Endogenous To Murine Spleen, Sawang Petvises, Helen O'Neill Feb 2014

Characterisation Of Dendritic Cells Arising From Progenitors Endogenous To Murine Spleen, Sawang Petvises, Helen O'Neill

Helen O'Neill

Heterogeneity amongst dendritic cell (DC) subsets leads to a spectrum of immune response capacity against pathogens. Several DC subsets in spleen have been described which differ in terms of phenotype and function. We have previously reported a distinct population of CD11cloCD11b hiMHC-II-CD8- dendritic-like "L-DC" in murine spleen, which can also be generated in splenic stromal longterm cultures. Here, the ontogeny of L-DC development in perinatal mice has been compared with other known splenic DC subsets. Flow cytometric analysis has revealed the presence of L-DC at embryonic age (E)18.5 spleen, while plasmacytoid (p)DC and conventional (c)DC appear at 2 and 4 …


Spleen Stroma Maintains Progenitors And Supports Long-Term Hematopoiesis, Helen O'Neill, Kristin Griffiths, Pravin Periasamy, Rebecca Hinton, Sawang Petvises, Yingying Hey, Jonathan Tang Dec 2013

Spleen Stroma Maintains Progenitors And Supports Long-Term Hematopoiesis, Helen O'Neill, Kristin Griffiths, Pravin Periasamy, Rebecca Hinton, Sawang Petvises, Yingying Hey, Jonathan Tang

Helen O'Neill

Hematopoietic stem/progenitor cells (HSPC) differentiate in the context of stromal niches producing cells of multiple lineages. Limited success has been achieved in the past with induction of hematopoiesis in vitro. Previously, spleen long-term stromal cultures (LTC) were shown to continuously support restricted hematopoiesis for production of novel dendritic-like cells (LTC-DC). An in vivo equivalent dendritic cell type was then described which is specific for spleen. The in vivo counterpart cell was termed 'L-DC' and represents a dendritic-like CD11cloCD11bhiCD8α-MHC-II- cell which differs phenotypically and functionally from monocytes/macrophages and conventional and plasmacytoid DC. Splenic stroma is now shown to maintain HSPC and …


Characterisation Of The Effect Of Lps On Dc Subset Discrimination In Spleen., Kristin Griffiths, Jonathan Tan, Helen O'Neill Dec 2013

Characterisation Of The Effect Of Lps On Dc Subset Discrimination In Spleen., Kristin Griffiths, Jonathan Tan, Helen O'Neill

Helen O'Neill

The Gram-negative bacterial endotoxin lipopolysaccharide (LPS) is a potent inflammatory mediator and a leading cause of bacterial sepsis. While LPS is known to activate antigen-presenting cells, here we find that LPS down-regulates expression of CD11c and CD11b on splenic dendritic cell subsets, thus confounding the ability to identify these subsets following treatment. This has implications with regard to tracking the response to LPS in terms of the cell subsets involved, and should be considered whenever such studies are undertaken.


Development Of Two Distinct Dendritic-Like Apcs In The Context Of Splenic Stroma, Pravin Periasamy, Sawang Petvises, Helen O'Neill Feb 2013

Development Of Two Distinct Dendritic-Like Apcs In The Context Of Splenic Stroma, Pravin Periasamy, Sawang Petvises, Helen O'Neill

Helen O'Neill

Murine splenic stroma has been found to provide an in vitro niche for hematopoiesis of dendritic-like APC. Two distinct cell types have been characterized. The novel "L-DC" subset has cross-presenting capacity, leading to activation of CD8+ T cells, but not activating CD4+ T cells, which is consistent with their CD11cloCD11bhiMHC-II- phenotype. For L-DC, an equivalent tissue-specific APC has been found only in spleen. A second population of CD11chiCD11bloMHC-II+ cells resembling conventional dendritic cells (cDC) can activate both CD4 and CD8 T cells. Production of L-DC but not cDC-like cells is now shown to be dependent on contact between the L-DC …


Stroma-Dependent Development Of Two Dendritic-Like Cells Types With Distinct Antigen Presenting Capability, Pravin Periasamy, Helen O'Neill Dec 2012

Stroma-Dependent Development Of Two Dendritic-Like Cells Types With Distinct Antigen Presenting Capability, Pravin Periasamy, Helen O'Neill

Helen O'Neill

Dendritic cells (DC) represent a heterogeneous class of antigen presenting cells (APC). Previously we reported a distinct myeloid dendritic-like cell present in spleen, as an in vivo counterpart to cells produced in murine spleen long-term cultures (LTC-DC). These cells, named 'L-DC', were found to be functionally and phenotypically distinct from conventional (c)DC, plasmacytoid (p)DC and monocytes. These results suggested that spleen may represent a niche for development of L-DC from endogenous progenitors. Adult murine spleen has now been investigated for the presence of L-DC progenitors. Lineage-negative (Lin)-ckitlo and Lin-ckithi progenitor subsets were identified as candidate populations, and tested for ability …


Distinct Progenitor Origin Distinguishes A Lineage Of Dendritic-Like Cells In Spleen., Sawang Petvises, Helen O'Neill Dec 2012

Distinct Progenitor Origin Distinguishes A Lineage Of Dendritic-Like Cells In Spleen., Sawang Petvises, Helen O'Neill

Helen O'Neill

The dendritic cell (DC) compartment comprises subsets of cells with distinct phenotypes. Previously this lab reported methodology for hematopoiesis of dendritic-like cells in vitro dependent on a murine splenic stromal cell line (5G3). Co-cultures of lineage-depleted bone marrow (Lin- BM) over 5G3 continuously produced a distinct population of dendritic-like "L-DC" for up to 35 days. Here the progenitor of L-DC is investigated in relation to known BM-derived hematopoietic progenitors. It is shown here that L-DC-like cells also derive from the CD150+Flt3- long-term reconstituting-hematopoietic stem cells (HSC), and also from the Flt3+ multipotential progenitor subset in BM. Lin- BM co-cultures also …


Novel Splenic Antigen Presenting Cell Derive From A Lin-Ckitlo Progenitor, Pravin Periasamy, Jonanthan Tan, Helen O'Neill Dec 2012

Novel Splenic Antigen Presenting Cell Derive From A Lin-Ckitlo Progenitor, Pravin Periasamy, Jonanthan Tan, Helen O'Neill

Helen O'Neill

The main DC subsets in murine spleen arise from BMderived precursors. Recently, a novel APC type was described in spleen. To determine if spleen contains the progenitors of this subset, a stromal coculture system was used to assess candidate progenitors for their hematopoietic potential. Here, the progenitor of that subset is identified as a spleen endogenous Lin-c-kitlo hematopoietic progenitor and is most highly enriched among the Lin-c-kitloCD34+ subset. Dendritic-like cells produced in vitro functionally resemble the previously described in vivo equivalent subset with high endocytic capacity and capability for antigen-specific activation of CD8+ T cells but not CD4+ T cells.


Investigation Into The Prevalence Of A Novel Dendritic-Like Cell Subset In Vivo, Kristin Griffiths, Jonathan Tan, Helen O'Neill Dec 2012

Investigation Into The Prevalence Of A Novel Dendritic-Like Cell Subset In Vivo, Kristin Griffiths, Jonathan Tan, Helen O'Neill

Helen O'Neill

A novel dendritic-like cell subset termed L-DC was recently identified in murine spleen based on marker expression of a homogeneous cell population derived from long-term culture of neonatal spleen. The function of L-DC is distinct from other splenic dendritic and myeloid cell subsets because of their high endocytic capacity and their ability to cross-present antigen to CD8+ T cells. This paper shows the subset to be unique to spleen and blood, with a similar, but possibly functionally distinct subset also present in bone marrow. The prevalence of the subset is low; ~6% of all dendritic and myeloid cells in the …


An In Vitro Microenvironment That Supports The Development Of A Novel Dendritic Cell From Bone Marrow And Spleen Hsc, Pravin Periasamy, Helen O'Neill Dec 2011

An In Vitro Microenvironment That Supports The Development Of A Novel Dendritic Cell From Bone Marrow And Spleen Hsc, Pravin Periasamy, Helen O'Neill

Helen O'Neill

No abstract provided.


Tedchnical Advance: In Vitro Production Of Distinct Dendritic-Like Antigen Presenting Cells From Self-Renewing Hematopoietic Stem Cells, Rebecca Hinton, Helen O'Neill Dec 2011

Tedchnical Advance: In Vitro Production Of Distinct Dendritic-Like Antigen Presenting Cells From Self-Renewing Hematopoietic Stem Cells, Rebecca Hinton, Helen O'Neill

Helen O'Neill

No abstract provided.


Molecular Definition Of A Hematopoietic Niche In Spleen, Pravan Periasamy, Helen O'Neill Dec 2011

Molecular Definition Of A Hematopoietic Niche In Spleen, Pravan Periasamy, Helen O'Neill

Helen O'Neill

No abstract provided.


In Vitro Differentiation Of Novel Antigen Presenting Cells, Sawang Petvises, Pravin Periasamy, Helen O'Neill Dec 2011

In Vitro Differentiation Of Novel Antigen Presenting Cells, Sawang Petvises, Pravin Periasamy, Helen O'Neill

Helen O'Neill

No abstract provided.


Myelopoiesis In Spleen Producing Distinct Dendritic-Like Cells, Jonathan Tan, Helen O'Neill Dec 2011

Myelopoiesis In Spleen Producing Distinct Dendritic-Like Cells, Jonathan Tan, Helen O'Neill

Helen O'Neill

Dendritic cells (DC) represent a heterogeneous class of antigen presenting cells (APC). Previously we reported a distinct myeloid dendritic-like cell present in spleen, as an in vivo counterpart to cells produced in murine spleen long-term cultures (LTC-DC). These cells, named 'L-DC', were found to be functionally and phenotypically distinct from conventional (c)DC, plasmacytoid (p)DC and monocytes. These results suggested that spleen may represent a niche for development of L-DC from endogenous progenitors. Adult murine spleen has now been investigated for the presence of L-DC progenitors. Lineage-negative (Lin)-ckitlo and Lin-ckithi progenitor subsets were identified as candidate populations, and tested for ability …


Myelopoiesis Related To Perinatal Spleen, Rebecca Hinton, Sawang Petvises, Helen O'Neill Dec 2010

Myelopoiesis Related To Perinatal Spleen, Rebecca Hinton, Sawang Petvises, Helen O'Neill

Helen O'Neill

Adult murine spleen is known to have a major role in the development of dendritic cell (DC) subsets, including conventional DC and plasmacytoid DC. In this lab, long-term cultures (LTCs) established from murine spleen support continuous production of novel dendritic-like cells, termed LTC-DC. An in vivo equivalent subset also exists in spleen, namely L-DC. As co-cultures using LTC-derived splenic stroma support the outgrowth of L-DC from spleen and bone marrow sources, it is likely that spleen represents an important niche for DC development. To investigate the appearance of L-DC during ontogeny, spleen was isolated from embryonic and neonatal mice of …


Spleen As A Distinct Site For Dendritic Cell Haematopoiesis, Jonathan Tan, Helen O'Neill Dec 2010

Spleen As A Distinct Site For Dendritic Cell Haematopoiesis, Jonathan Tan, Helen O'Neill

Helen O'Neill

No abstract provided.


Identification Of A Novel Antigen Cross-Presenting Cell In Spleen: A Counterpart To Cells Produced In Long-Term Culture, Jonathan Tan, Ben Quah, Kristin Griffiths, Pravin Periasamy, Yingying Hey, Helen O'Neill Dec 2010

Identification Of A Novel Antigen Cross-Presenting Cell In Spleen: A Counterpart To Cells Produced In Long-Term Culture, Jonathan Tan, Ben Quah, Kristin Griffiths, Pravin Periasamy, Yingying Hey, Helen O'Neill

Helen O'Neill

Antigen-presenting cells (APC), like dendritic cells (DC), are essential for T-cell activation, leading to immunity or tolerance. Multiple DC subsets each play a unique role in the immune response. Here, a novel splenic dendritic-like APC has been characterized in mice that has immune function and cell surface phenotype distinct from other, described DC subsets. These were identified as a cell type continuously produced in spleen long-term cultures (LTC) and have anin vivoequivalent cell type in mice, namely 'L-DC'. This study characterizes LTC-DC in terms of marker phenotype and function, and compares them with L-DC and other known splenic DC and …