Submitted October 31, 2007
Accepted March 21, 2008
Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T cell responses
Helen Karlsson*, Sujith Samarasinghe, Lynne M Ball, Berit Sundberg, Arjan C Lankester, Francesco Dazzi, Mehmet Uzunel, Kanchan Rao, Paul Veys, Katarina Le Blanc, Olle Ringden, and Persis J. Amrolia
Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
Pediatrics, Leiden University Medical Centre, Leiden, Netherlands
Clinical Immunology and Transfusion Medicine, Karolinska Institute, Stockholm, Sweden
Haematology, Imperial College London, London, United Kingdom
Bone Marrow Transplantation, Great Ormond Street Hospital, London, United Kingdom
* Corresponding author; email: h.karlsson{at}ich.ucl.ac.uk.
Mesenchymal stem cells (MSC) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSC appears a promising therapy for graft-versus-host-disease (GvHD). Little is known about the specificity of immunosuppression by MSC, in particular the effect on immunity to pathogens. We have studied how MSC affect Epstein-Barr virus (EBV) and cytomegalovirus (CMV)-specific T-cell responses. We found that EBV and CMV-induced proliferation and interferon-
(IFN-) production from peripheral blood mononuclear cells (PBMC) was less affected by third-party MSC than the response to alloantigen and that MSC 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 MSC retained the ability to proliferate and produce IFN- in response to their cognate antigen and to kill virally infected targets. Finally, PBMC from 2 patients who received MSC for acute GvHD showed persistence of CMV-specific T-cells and retained IFN- response to CMV post MSC infusion. In summary, MSC 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 MSC and suggest that the effector functions of virus-specific T-cells may be retained after MSC infusion.
