title: Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses.
abstract: 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.
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, London, United Kingdom. helen.a.karlsson@karolinska.se
authors.forename: Helen
authors.initials: H
authors.lastname: Karlsson
authors.forename: Sujith
authors.initials: S
authors.lastname: Samarasinghe
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ball
authors.forename: Berit
authors.initials: B
authors.lastname: Sundberg
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uzunel
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Persis J
authors.initials: PJ
authors.lastname: Amrolia
mesh_terms: D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology; D006086:Graft vs Host Disease / Q000628:therapy; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D014780:Viruses / Q000276:immunology
chemical_list: D007519:Isoantigens