Mesenchymal stem cells (MSCs) have been suggested play an important role in modulating cell-mediated immunity. In the setting of transplantation, allogeneic MSCs could mediate suppressive effects or stimulate an alloimmune response. The aim of this study was to define the surface phenotype of human allogeneic MSCs and their potential effects on modulating allospecific memory T cell responses and primed T cell proliferation to alloantigens. Human bone marrow derived MSCs were studied by polychromatic flow cytometry with and without TNF-a or IFN-g stimulation. Mixed lymphocyte responses were performed using human PBMCs stimulated by allogeneic mature dendritic cells (mDCs) in the presence or absence of MSCs interrogated using flow cytometry. TNF-a or IFN-γ stimulated-MSCs showed significant upregulation of CD40, CD54, PD-1 ligand I, HLA-ABC, and HLA-DR when compared to resting MSCs (p<0.05). CD58, PD-1 ligand II, and B7 molecules were not seen on stimulated MSCs. Additionally, mDCs induced strong CD4⁺ and CD8⁺ cell proliferation characterized as predominantly PD1⁺/C57⁺, CD2^high, and memory cells (CCR7⁺CD45RA^–, CCR7^–CD45RA⁺, CCR7^–CD45RA^–). In contrast, T cell proliferation in response to MSCs was negligible. Most importantly, mDC-induced T cell proliferation was significantly inhibited in the presence of allogeneic MSCs (90.73±2.36% in CD4, p=0.0002 and 77.37±3.47% in CD8, p=0.0119). Furthermore, mDC-stimulated T cell proliferation was only partially inhibited (69.78±7.32% in CD4, p=0.0035 and 60.02±4.46% in CD8, p=0.0425) when MSCs were separated from the reaction using a transwell system, indicating that cell-cell contact was partially involved in the effect. The allo-specific dual-cytokine (TNF-⍺/IFN-γ) producing memory CD8+ cells were detected following stimulation with mDCs, and the presence of MSC partially inhibited activation of allo-specific memory T cells. In summary, bone marrow derived MSCs, following cytokine stimulation, upregulate major costimulation and adhesion, PD-1 ligand II, and HLA class I and II expression but not B7 expression. Allogeneic MSCs poorly stimulate T cell proliferation, and suppress allogeneic mDCs-induced T cell proliferation via both contact-dependent and contract-independent mechanisms. Our findings suggest that allogeneic MSCs may suppress allospecific T cell immunity rather than leading to alloimmunization.

CITATION INFORMATION: Gao Q., Kirk A., Xu H. Characterization of Mesenchymal Stem Cell Phenotype and Its Immunomodulatory Effects during Allo-Specific T Cell Immune-Responses Am J Transplant. 2017;17 (suppl 3).

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