title: Mesenchymal stromal cells inhibit proliferation of virus-specific CD8(+) T cells.
abstract: Mesenchymal stromal cells (MSCs) possess broad immunomodulatory capacities that are currently investigated for potential clinical application in treating autoimmune disorders. Third-party MSCs suppress alloantigen-induced proliferation of peripheral blood mononuclear cells providing the rationale for clinical use in graft-versus-host disease (GvHD). We confirmed that MSCs strongly inhibited proliferation of CD8(+) T cells in a mixed lymphocyte reaction. However, MSCs also suppressed proliferation of T cells specifically recognizing cytomegalovirus (CMV) and influenza virus. Inhibition was dose dependent, but independent of the culture medium. MSCs inhibited proliferation of specific CD8(+) T cells and the release of IFN-γ by specific CD8(+) T cells for immunodominant HLA-A2- and HLA-B7- restricted antigen epitopes derived from CMV phosphoprotein 65 and influenza matrix protein. This is in contrast to a recently reported scenario where MSCs exert differential effects on alloantigen and virus-specific T cells potentially having an impact on surveillance and prophylaxis of patients treated by MSCs.
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Malcherek
authors.affiliation: 1] Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany [2] Department of Hematology, ZhongDa Hospital, Southeast University, Nanjing, PR China.
authors.forename: N
authors.initials: N
authors.lastname: Jin
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: A G
authors.initials: AG
authors.lastname: Hückelhoven
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Mani
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Gern
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Diehlmann
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Wuchter
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Hematology, ZhongDa Hospital, Southeast University, Nanjing, PR China.
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Department of Internal Medicine V, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010750:Phosphoproteins / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology; D014780:Viruses / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007519:Isoantigens; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma