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: G Malcherek, N Jin, A G Hückelhoven, J Mani, L Wang, U Gern, A Diehlmann, P Wuchter, A Schmitt, B Chen, A D Ho, M Schmitt
• Journal: Leukemia (Leukemia) Vol. 28 Issue 12 Pg. 2388-94 (Dec 2014) ISSN: 1476-5551 [Electronic] England
• PMID: 25227910 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Immunodominant Epitopes
• Isoantigens
• Phosphoproteins
• Viral Matrix Proteins
• cytomegalovirus matrix protein 65kDa
• Interferon-gamma

Topics

• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Immunodominant Epitopes (immunology)
• Interferon-gamma (biosynthesis)
• Isoantigens (immunology)
• Lymphocyte Activation (immunology)
• Mesenchymal Stem Cells (metabolism)
• Phosphoproteins (immunology)
• T-Cell Antigen Receptor Specificity (immunology)
• Viral Matrix Proteins (immunology)
• Viruses (immunology)