Development of two distinct dendritic-like APCs in the context of splenic stroma

Pravin Periasamy, Sawang Petvises, Helen C O'Neill

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

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 CD11c(lo)CD11b(hi)MHC-II(-) phenotype. For L-DC, an equivalent tissue-specific APC has been found only in spleen. A second population of CD11c(hi)CD11b(lo)MHC-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 progenitor and stroma such that the presence of a Transwell membrane can prevent L-DC development. Since L-DC can be produced continuously in vitro in stromal co-cultures overlaid with bone marrow (BM) progenitors, it was hypothesized that L-DC progenitors are self-renewing. The L-DC progenitor is shown here to be defined by the Flt3(-)c-kit(+)Lin(-)Sca-1(+) (F(-)KLS) subset of adult BM which contains primitive HSC. Since the less primitive F(+)KLS HSC subset also contains L-DC progenitors, Flt3 does not appear to be a defining marker for this progenitor. Precursors of the cDC-like subset are found only within the F(+)KLS subset and seed production of a transient population of APC. All data identify differentiation of L-DC from HSC, and of cDC-like cells from DC precursors, which occurs independently of inflammatory signals and is dependent on a splenic stromal microenvironment.

Original languageEnglish
Pages (from-to)73
JournalFrontiers in Immunology
Volume4
DOIs
Publication statusPublished - 2013
Externally publishedYes

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Dendritic Cells
T-Lymphocytes
Bone Marrow
Hematopoiesis
Coculture Techniques
Population
Seeds
Spleen
Phenotype
Membranes
In Vitro Techniques

Cite this

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title = "Development of two distinct dendritic-like APCs in the context of splenic stroma",
abstract = "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 CD11c(lo)CD11b(hi)MHC-II(-) phenotype. For L-DC, an equivalent tissue-specific APC has been found only in spleen. A second population of CD11c(hi)CD11b(lo)MHC-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 progenitor and stroma such that the presence of a Transwell membrane can prevent L-DC development. Since L-DC can be produced continuously in vitro in stromal co-cultures overlaid with bone marrow (BM) progenitors, it was hypothesized that L-DC progenitors are self-renewing. The L-DC progenitor is shown here to be defined by the Flt3(-)c-kit(+)Lin(-)Sca-1(+) (F(-)KLS) subset of adult BM which contains primitive HSC. Since the less primitive F(+)KLS HSC subset also contains L-DC progenitors, Flt3 does not appear to be a defining marker for this progenitor. Precursors of the cDC-like subset are found only within the F(+)KLS subset and seed production of a transient population of APC. All data identify differentiation of L-DC from HSC, and of cDC-like cells from DC precursors, which occurs independently of inflammatory signals and is dependent on a splenic stromal microenvironment.",
author = "Pravin Periasamy and Sawang Petvises and O'Neill, {Helen C}",
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Development of two distinct dendritic-like APCs in the context of splenic stroma. / Periasamy, Pravin; Petvises, Sawang; O'Neill, Helen C.

In: Frontiers in Immunology, Vol. 4, 2013, p. 73.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Development of two distinct dendritic-like APCs in the context of splenic stroma

AU - Periasamy, Pravin

AU - Petvises, Sawang

AU - O'Neill, Helen C

PY - 2013

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N2 - 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 CD11c(lo)CD11b(hi)MHC-II(-) phenotype. For L-DC, an equivalent tissue-specific APC has been found only in spleen. A second population of CD11c(hi)CD11b(lo)MHC-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 progenitor and stroma such that the presence of a Transwell membrane can prevent L-DC development. Since L-DC can be produced continuously in vitro in stromal co-cultures overlaid with bone marrow (BM) progenitors, it was hypothesized that L-DC progenitors are self-renewing. The L-DC progenitor is shown here to be defined by the Flt3(-)c-kit(+)Lin(-)Sca-1(+) (F(-)KLS) subset of adult BM which contains primitive HSC. Since the less primitive F(+)KLS HSC subset also contains L-DC progenitors, Flt3 does not appear to be a defining marker for this progenitor. Precursors of the cDC-like subset are found only within the F(+)KLS subset and seed production of a transient population of APC. All data identify differentiation of L-DC from HSC, and of cDC-like cells from DC precursors, which occurs independently of inflammatory signals and is dependent on a splenic stromal microenvironment.

AB - 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 CD11c(lo)CD11b(hi)MHC-II(-) phenotype. For L-DC, an equivalent tissue-specific APC has been found only in spleen. A second population of CD11c(hi)CD11b(lo)MHC-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 progenitor and stroma such that the presence of a Transwell membrane can prevent L-DC development. Since L-DC can be produced continuously in vitro in stromal co-cultures overlaid with bone marrow (BM) progenitors, it was hypothesized that L-DC progenitors are self-renewing. The L-DC progenitor is shown here to be defined by the Flt3(-)c-kit(+)Lin(-)Sca-1(+) (F(-)KLS) subset of adult BM which contains primitive HSC. Since the less primitive F(+)KLS HSC subset also contains L-DC progenitors, Flt3 does not appear to be a defining marker for this progenitor. Precursors of the cDC-like subset are found only within the F(+)KLS subset and seed production of a transient population of APC. All data identify differentiation of L-DC from HSC, and of cDC-like cells from DC precursors, which occurs independently of inflammatory signals and is dependent on a splenic stromal microenvironment.

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DO - 10.3389/fimmu.2013.00073

M3 - Article

VL - 4

SP - 73

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

ER -