Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation

Patrizia Comoli, Fabrizio Ginevri, Rita MacCario, Maria Antonietta Avanzini, Massimo Marconi, Antonella Groff, Angela Cometa, Michela Cioni, Laura Porretti, Walter Barberi, Francesco Frassoni, Franco Locatelli

Research output: Contribution to journalArticle

Abstract

Background. Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease. Methods. To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody. Results. We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. Conclusions. Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients.

Original languageEnglish
Pages (from-to)1196-1202
Number of pages7
JournalNephrology Dialysis Transplantation
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Mesenchymal Stromal Cells
Antibody Formation
Lymphocytes
Immunoglobulins
In Vitro Techniques
CD40 Ligand
Isoantigens
Immunoglobulin Isotypes
Interleukin-5
Organ Transplantation
Graft vs Host Disease
Graft Survival
Chronic Kidney Failure
Dialysis
Blood Cells
B-Lymphocytes
Animal Models
Transplantation
Monoclonal Antibodies
Tissue Donors

Keywords

  • Alloantigen-specific Ig
  • Humoral immune response
  • Kidney transplantation
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Nephrology
  • Transplantation
  • Medicine(all)

Cite this

Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. / Comoli, Patrizia; Ginevri, Fabrizio; MacCario, Rita; Avanzini, Maria Antonietta; Marconi, Massimo; Groff, Antonella; Cometa, Angela; Cioni, Michela; Porretti, Laura; Barberi, Walter; Frassoni, Francesco; Locatelli, Franco.

In: Nephrology Dialysis Transplantation, Vol. 23, No. 4, 04.2008, p. 1196-1202.

Research output: Contribution to journalArticle

Comoli, Patrizia ; Ginevri, Fabrizio ; MacCario, Rita ; Avanzini, Maria Antonietta ; Marconi, Massimo ; Groff, Antonella ; Cometa, Angela ; Cioni, Michela ; Porretti, Laura ; Barberi, Walter ; Frassoni, Francesco ; Locatelli, Franco. / Human mesenchymal stem cells inhibit antibody production induced in vitro by allostimulation. In: Nephrology Dialysis Transplantation. 2008 ; Vol. 23, No. 4. pp. 1196-1202.
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abstract = "Background. Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease. Methods. To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody. Results. We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. Conclusions. Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients.",
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AU - Comoli, Patrizia

AU - Ginevri, Fabrizio

AU - MacCario, Rita

AU - Avanzini, Maria Antonietta

AU - Marconi, Massimo

AU - Groff, Antonella

AU - Cometa, Angela

AU - Cioni, Michela

AU - Porretti, Laura

AU - Barberi, Walter

AU - Frassoni, Francesco

AU - Locatelli, Franco

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N2 - Background. Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease. Methods. To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody. Results. We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. Conclusions. Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients.

AB - Background. Antibodies directed against alloantigens are implicated in the pathogenesis of several immune reactions complicating transplantation, including humoral rejection after solid organ transplantation. Mesenchymal stem cells (MSCs) have immunomodulatory capacity, since in vivo they may prolong skin graft survival in the animal model and can rescue patients with life-threatening graft-versus-host disease. Methods. To investigate whether MSCs exert an inhibitory effect on antibody production during allostimulation, we stimulated peripheral blood mononuclear cells, obtained from healthy controls or sensitized patients undergoing dialysis for end-stage renal failure, in mixed lymphocyte culture (MLC), and evaluated immunoglobulin production either in the absence or in the presence of third-party allogeneic MSCs. We also evaluated the effect of MSCs on B-cell allostimulation performed adding to MLC a polyclonal stimulus delivered by an agonist anti-CD40 monoclonal antibody. Results. We found that the addition of MSCs at the beginning of MLC considerably inhibited immunoglobulin production in standard MLC, irrespective of the MSC dose employed. Conversely, immunoglobulin secretion induced by direct CD40-CD40L binding was not significantly inhibited. Furthermore, we demonstrated, in one sensitized patient, that secretion of donor-specific anti-HLA class I antibodies detected both in baseline serum and in the supernatant of control MLC was inhibited by the addition of MSCs. Mechanistically, the addition of MSCs induced a striking decrease of IL-5 production in the cultures. Conclusions. Our findings suggest that third-party MSC are able to suppress allo-specific antibody production in vitro, and may therefore help overcome a positive cross-match in sensitized transplant recipients.

KW - Alloantigen-specific Ig

KW - Humoral immune response

KW - Kidney transplantation

KW - Mesenchymal stem cells

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