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Full-Text Articles in Medicine and Health Sciences

In Vitro Haematopoiesis Of A Novel Dendritic-Like Cell Present In Murine Spleen, Jonathan Tan, Helen O'Neill Oct 2015

In Vitro Haematopoiesis Of A Novel Dendritic-Like Cell Present In Murine Spleen, Jonathan Tan, Helen O'Neill

Jonathan Tan

Abstract: Dendritic cells (DC) are important antigen presenting cells (APC) which induce and control the adaptive immune response. In spleen alone, multiple DC subsets can be distinguished by cell surface marker phenotype. Most of these have been shown to develop from progenitors in bone marrow and to seed lymphoid and tissue sites during development. This study advances in vitro methodology for haematopoiesis of dendritic-like cells from progenitors in spleen. Since spleen progenitors undergo differentiation in vitro to produce these cells, the possibility exists that spleen represents a specific niche for differentiation of this subset. The fact that an equivalent cell …


Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill Sep 2015

Haematopoietic Stem Cells In Spleen Have Distinct Differentiative Potential For Antigen Presenting Cells., Jonathan Tan, Helen O'Neill

Jonathan Tan

Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice …


Spleen As A Distinct Site For Dendritic Cell Haematopoiesis, Jonathan Tan, Helen O'Neill Jul 2015

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

Jonathan Tan

No abstract provided.


Murine Spleen Tissue Regeneration From Neonatal Spleen Capsule Requires Lymphotoxin Priming Of Stromal Cells, Jonathan Tan, Takeshi Watanabe Dec 2013

Murine Spleen Tissue Regeneration From Neonatal Spleen Capsule Requires Lymphotoxin Priming Of Stromal Cells, Jonathan Tan, Takeshi Watanabe

Jonathan Tan

Spleen is a tissue with regenerative capacity, which allows autotransplantation of human spleen fragments to counteract the effects of splenectomy. We now reveal in a murine model that transplant of neonatal spleen capsule alone leads to the regeneration of full spleen tissue. This finding indicates that graft-derived spleen stromal cells, but not lymphocytes, are essential components of tissue neogenesis, a finding verified by transplant and regeneration of Rag1KO spleen capsules.We further demonstrate that lymphotoxin and lymphoid tissue inducer cells participate in two key elements of spleen neogenesis, bulk tissue regeneration and white pulp organization, identifying a lymphotoxin-dependent pathway for neonatal …


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

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

Jonathan Tan

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 CD11cloCD11bhiCD8a-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

Jonathan Tan

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.


Novel Splenic Antigen-Presenting Cells Derive From A Lin-C-Kitlo Progenitor, Pravin Periasamy, Jonathan Tan, Helen O'Neill Dec 2012

Novel Splenic Antigen-Presenting Cells Derive From A Lin-C-Kitlo Progenitor, Pravin Periasamy, Jonathan Tan, Helen O'Neill

Jonathan Tan

No abstract provided.


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

Jonathan Tan

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 …


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

Jonathan Tan

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 …


Spleen As A Site For Hematopoiesis Of A Distinct Antigen Presenting Cell Type, Helen O'Neill, Kristin Griffiths, Pravin Periasamy, Rebecca Hinton, Ying-Ying Hey, Sawang Petvises, Jonathan Tan Dec 2010

Spleen As A Site For Hematopoiesis Of A Distinct Antigen Presenting Cell Type, Helen O'Neill, Kristin Griffiths, Pravin Periasamy, Rebecca Hinton, Ying-Ying Hey, Sawang Petvises, Jonathan Tan

Jonathan Tan

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a …


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

Jonathan Tan

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 …


Artificial Engineering Of Secondary Lymphoid Organs, Jonathan Tan, Takeshi Watanabe Dec 2009

Artificial Engineering Of Secondary Lymphoid Organs, Jonathan Tan, Takeshi Watanabe

Jonathan Tan

Secondary lymphoid organs such as spleen and lymph nodes are highly organized immune structures essential for the initiation of immune responses. They display distinct B cell and T cell compartments associated with specific stromal follicular dendritic cells and fibroblastic reticular cells, respectively. Interweaved through the parenchyma is a conduit system that distributes small antigens and chemokines directly to B and T cell zones. While most structural aspects between lymph nodes and spleen are common, the entry of lymphocytes, antigen-presenting cells, and antigen into lymphoid tissues is regulated differently, reflecting the specialized functions of each organ in filtering either lymph or …