Abstract
Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and anti-inflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs+CpG. Inhibition is restored in CpG+MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4+ and CD8+ cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.
| Original language | English |
|---|---|
| Pages (from-to) | 93-103 |
| Number of pages | 11 |
| Journal | Stem Cells and Development |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2015 |
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ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Hematology
Cite this
Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells. / Rosado, Maria Manuela; Bernardo, Maria Ester; Scarsella, Marco; Conforti, Antonella; Giorda, Ezio; Biagini, Simone; Cascioli, Simona; Rossi, Francesca; Guzzo, Isabella; Vivarelli, Marina; Dello Strologo, Luca; Emma, Francesco; Locatelli, Franco; Carsetti, Rita.
In: Stem Cells and Development, Vol. 24, No. 1, 01.01.2015, p. 93-103.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells
AU - Rosado, Maria Manuela
AU - Bernardo, Maria Ester
AU - Scarsella, Marco
AU - Conforti, Antonella
AU - Giorda, Ezio
AU - Biagini, Simone
AU - Cascioli, Simona
AU - Rossi, Francesca
AU - Guzzo, Isabella
AU - Vivarelli, Marina
AU - Dello Strologo, Luca
AU - Emma, Francesco
AU - Locatelli, Franco
AU - Carsetti, Rita
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and anti-inflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs+CpG. Inhibition is restored in CpG+MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4+ and CD8+ cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.
AB - Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and anti-inflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs+CpG. Inhibition is restored in CpG+MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4+ and CD8+ cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.
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UR - http://www.scopus.com/inward/citedby.url?scp=84919782445&partnerID=8YFLogxK
U2 - 10.1089/scd.2014.0155
DO - 10.1089/scd.2014.0155
M3 - Article
C2 - 25036865
AN - SCOPUS:84919782445
VL - 24
SP - 93
EP - 103
JO - Stem Cells and Development
JF - Stem Cells and Development
SN - 1547-3287
IS - 1
ER -