Karlsson, H and Samarasinghe, S and Ball, LM and Sundberg, B and Lankester, AC and Dazzi, F and Uzunel, M and Rao, K and Veys, P and Le Blanc, K and Ringdén, O and Amrolia, PJ (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood , 112 (3) 532 - 541. 10.1182/blood-2007-10-119370.
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Mesenchymal stem cells (MSCs) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSCs seems to be a promising therapy for graft-versus-host disease (GVHD). Little is known about the specificity of immunosuppression by MSCs, in particular the effect on immunity to pathogens. We have studied how MSCs affect T-cell responses specific to Epstein-Barr virus (EBV) and cytomegalovirus (CMV). We found that EBV- and CMV-induced proliferation and interferon-gamma (IFN-gamma) production from peripheral blood mononuclear cells (PBMCs) was less affected by third-party MSCs than the response to alloantigen and that MSCs had no effect on expansion of EBV and CMV pentamer-specific T cells. Established EBV-specific cytotoxic T cells (CTL) or CMV-CTL cultured with MSCs retained the ability to proliferate and produce IFN-gamma in response to their cognate antigen and to kill virally infected targets. Finally, PBMCs from 2 patients who received MSCs for acute GVHD showed persistence of CMV-specific T cells and retained IFN-gamma response to CMV after MSC infusion. In summary, MSCs have little effect on T-cell responses to EBV and CMV, which contrasts to their strong immunosuppressive effects on alloreactive T cells. These data have major implications for immunotherapy of GVHD with MSCs and suggest that the effector functions of virus-specific T cells may be retained after MSC infusion.
|Title:||Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses.|
|Keywords:||Child, Child, Preschool, Cytomegalovirus, Graft vs Host Disease, Herpesvirus 4, Human, Humans, Isoantigens, Male, Mesenchymal Stem Cell Transplantation, Mesenchymal Stromal Cells, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Viruses|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Infection and Immunity > ICH - Molecular Immunology Unit|
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