Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses.
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.
Karlsson
Helen
H
Molecular Immunology Unit, Institute of Child Health, London, United Kingdom. helen.a.karlsson@karolinska.se
Samarasinghe
Sujith
S
Ball
Lynne M
LM
Sundberg
Berit
B
Lankester
Arjan C
AC
Dazzi
Francesco
F
Uzunel
Mehmet
M
Rao
Kanchan
K
Veys
Paul
P
Le Blanc
Katarina
K
Ringdén
Olle
O
Amrolia
Persis J
PJ
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
D007519:Isoantigens