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Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells (MSCs)
06:20

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Published on: December 24, 2015

Mesenchymal stem cells control alloreactive CD8(+) CD28(-) T cells.

A U Engela1, C C Baan, N H R Litjens

  • 1Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Clinical and Experimental Immunology
|September 14, 2013
PubMed
Summary
This summary is machine-generated.

Mesenchymal stem cells (MSC) can control pathogenic CD8(+) CD28(-) T-cells, which are resistant to belatacept treatment in kidney transplant patients. This suggests a potential combination therapy for preventing alloreactivity.

Keywords:
CD8 T cellsco-stimulation/co-stimulatory moleculesimmune regulationstem cells

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Area of Science:

  • Immunology
  • Transplantation Immunology
  • Cell Therapy

Background:

  • Belatacept, a CD28/B7 co-stimulation blocker, is used to prevent kidney transplant rejection.
  • CD8(+) CD28(-) T-cells possess pathogenic properties and are unresponsive to belatacept.
  • Mesenchymal stem cells (MSC) are investigated for their potential to control these resistant T-cells.

Purpose of the Study:

  • To investigate the efficacy of mesenchymal stem cells (MSC) in controlling pathogenic CD8(+) CD28(-) T-cells.
  • To evaluate the combined effect of MSC and belatacept on T-cell proliferation and alloreactivity.

Main Methods:

  • Mixed lymphocyte reactions (MLR) were used to assess T-cell proliferation.
  • Peripheral blood mononuclear cells (PBMC) were treated with varying concentrations of MSC and belatacept.
  • Flow cytometry was employed to analyze T-cell populations and CD28 expression.

Main Results:

  • Both MSC and belatacept inhibited PBMC proliferation in a dose-dependent manner.
  • MSC significantly reduced the percentage of CD8(+) CD28(-) T-cells in proliferating populations (45.9%).
  • MSC controlled pre-existing CD8(+) CD28(-) T-cells, while belatacept did not affect their proliferation.

Conclusions:

  • Mesenchymal stem cells (MSC) effectively inhibit alloreactive CD8(+) CD28(-) T-cells resistant to belatacept.
  • A combination therapy of MSC and belatacept shows promise for controlling alloreactivity in kidney transplantation.