Abstract
The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts display a differentiated myofibroblast phenotype and constitutively express a biologically active form of membrane interleukin (IL)-15 that can drive co-cultured CD34+ blood cells to differentiate into activated natural killer (NK) cells. Here, we show that, in addition to NK cells, CD34/fibroblast co-cultures also yield myeloid CD1a+CD38 +CD68+CD86+ HLA-DR+CD14 -CD80- dendritic cells (DCs) after 3-4 weeks in culture. We found that DC development depended on endogenously secreted stromal macrophage colony-stimulating factor (M-CSF) and CD40/CD40L interaction rather than on fibroblast- and CD34-derived membrane IL-15. CD1a+ cells were necessary for co-produced NK cells to acquire lytic functions by a mechanism involving cell-to-cell contact and DC-derived IL-12. This study highlights the importance of spleen myofibroblasts in the in vitro generation of two distinct cell types (DC and NK cells) from the innate immune system and suggests that the human spleen is involved in the generation of NK cells from circulating progenitors.
| Original language | English |
|---|---|
| Pages (from-to) | 265-273 |
| Number of pages | 9 |
| Journal | Clinical and Experimental Immunology |
| Volume | 140 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - May 2005 |
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Keywords
- Blood progenitor
- Dendritic cell
- Immune regulation
- Myofibroblast
- Natural killer cell
ASJC Scopus subject areas
- Immunology
Cite this
Importance of stromal determinants in the generation of dendritic and natural killer cells in the human spleen. / Briard, D.; Azzarone, B.; Brouty-Boyé, Danièle.
In: Clinical and Experimental Immunology, Vol. 140, No. 2, 05.2005, p. 265-273.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Importance of stromal determinants in the generation of dendritic and natural killer cells in the human spleen
AU - Briard, D.
AU - Azzarone, B.
AU - Brouty-Boyé, Danièle
PY - 2005/5
Y1 - 2005/5
N2 - The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts display a differentiated myofibroblast phenotype and constitutively express a biologically active form of membrane interleukin (IL)-15 that can drive co-cultured CD34+ blood cells to differentiate into activated natural killer (NK) cells. Here, we show that, in addition to NK cells, CD34/fibroblast co-cultures also yield myeloid CD1a+CD38 +CD68+CD86+ HLA-DR+CD14 -CD80- dendritic cells (DCs) after 3-4 weeks in culture. We found that DC development depended on endogenously secreted stromal macrophage colony-stimulating factor (M-CSF) and CD40/CD40L interaction rather than on fibroblast- and CD34-derived membrane IL-15. CD1a+ cells were necessary for co-produced NK cells to acquire lytic functions by a mechanism involving cell-to-cell contact and DC-derived IL-12. This study highlights the importance of spleen myofibroblasts in the in vitro generation of two distinct cell types (DC and NK cells) from the innate immune system and suggests that the human spleen is involved in the generation of NK cells from circulating progenitors.
AB - The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts display a differentiated myofibroblast phenotype and constitutively express a biologically active form of membrane interleukin (IL)-15 that can drive co-cultured CD34+ blood cells to differentiate into activated natural killer (NK) cells. Here, we show that, in addition to NK cells, CD34/fibroblast co-cultures also yield myeloid CD1a+CD38 +CD68+CD86+ HLA-DR+CD14 -CD80- dendritic cells (DCs) after 3-4 weeks in culture. We found that DC development depended on endogenously secreted stromal macrophage colony-stimulating factor (M-CSF) and CD40/CD40L interaction rather than on fibroblast- and CD34-derived membrane IL-15. CD1a+ cells were necessary for co-produced NK cells to acquire lytic functions by a mechanism involving cell-to-cell contact and DC-derived IL-12. This study highlights the importance of spleen myofibroblasts in the in vitro generation of two distinct cell types (DC and NK cells) from the innate immune system and suggests that the human spleen is involved in the generation of NK cells from circulating progenitors.
KW - Blood progenitor
KW - Dendritic cell
KW - Immune regulation
KW - Myofibroblast
KW - Natural killer cell
UR - http://www.scopus.com/inward/record.url?scp=17644378124&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17644378124&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2249.2005.02792.x
DO - 10.1111/j.1365-2249.2005.02792.x
M3 - Article
VL - 140
SP - 265
EP - 273
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
SN - 0009-9104
IS - 2
ER -