Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Function of Allogeneic Activated Vγ9Vδ2 T Lymphocytes In Vitro

Abstract

Background. Human umbilical cord mesenchymal stem cells (UC-MSCs) can regulate the function of immune cells. However, whether and how UC-MSCs can modulate the function of Vγ9Vδ2 T cells has not been fully understood. Methods. The PBMCs or Vγ9Vδ2 T cells were activated and expanded with pamidronate (PAM) and interleukin-2 (IL-2) with or without the presence UC-MSCs. The effects of UC-MSCs on the proliferation, cytokine expression, and cytotoxicity of Vγ9Vδ2 T cells were determined by flow cytometry. The effects of UC-MSCs on Fas-L, TRAIL-expressing Vγ9Vδ2 T cells, and Vγ9Vδ2 T cell apoptosis were determined by flow cytometry. Results. UC-MSCs inhibited Vγ9Vδ2 T cell proliferation in a dose-dependent but cell-contact independent manner. Coculture with UC-MSCs reduced the frequency of IFNγ+ but increased granzyme B+ Vγ9Vδ2 T cells. UC-MSCs inhibited the cytotoxicity of Vγ9Vδ2 T cells against influenza virus H1N1 infected A549 cells and also reduced the frequency of Fas-L+, TRAIL+ Vγ9Vδ2 T cells but failed to modulate the apoptosis of Vγ9Vδ2 T cells. Conclusions. These results indicated that UC-MSCs efficiently suppressed the proliferation and cytotoxicity of Vγ9Vδ2 T cells and modulated their cytokine production. Fas-L and TRAIL were involved in the regulation. Cell contact and apoptosis of Vγ9Vδ2 T cells were not necessary for the inhibition.

Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19

“…For example, MSCs suppress lymphocyte proliferation in response to the activation of influenza-specific T cells in vitro [17]. Umbilical cord-derived MSCs (UC-MSCs) have also been shown to inhibit the cytotoxicity of specific T cells against H1N1 influenza virus in vitro, [18] leading perhaps to prolonged infection in recipients. This is in contrast to reports where, for example, in models of CMV infection, MSCs exert differential effects on alloantigen and virus specific T cells that retain the ability to proliferate, produce IFN-, and to kill CMV-infected cells in vitro.…”

Mesenchymal Stromal Cells and Viral Infection

“…The dual effects of MSCs on immune response were later confirmed by Li et al in which IDO is responsible for switching an immune-modulator to immune-enhancer [ 68 ]. According to these dual effects, the drawbacks of immune regulatory action of MSCs in the infectious environment have been reported; for example, (i) Sundin et al demonstrated that lymphocyte proliferation induced by CMV antigen was suppressed in the presence of MSCs [ 57 ], (ii) Malcherek et al found that MSCs suppressed proliferation and the release of IFN- γ of CMV and influenza-specific T cells [ 58 ], and (iii) UC-MSCs were recently shown to inhibit the cytotoxicity of V γ 9V δ 2 T cells against H1N1 influenza virus in vitro [ 59 ], supporting the evidences of prolonged infection in recipients. Thus, this is important for medical specialists to be aware of dual effects of MSCs on immune system against viral infection in using MSCs as regenerative medicine.…”

The rationale of using mesenchymal stem cells in patients with COVID-19-related acute respiratory distress syndrome: What to expect

“…51 UC-MSCs are positive for CD73, CD90, CD105, and human leukocyte antigen (HLA) class I and negative for CD45 and HLA-DR. 36,52 They display immunosuppressive potential by cell-cell contact with activated T cells, 53 and they efficiently suppress the proliferation and cytokine production of a subset of circulating T cells. 54 Moreover, UC-MSCs produce large amounts of tolerogenic IL-6, transforming growth factor (TGF)-β, and VEGF-1. 55 Given that UC-MSCs exhibit many unique features, involving the regulation of both innate and adaptive immune responses, 56 they stand as the most widely used and first-selected allogeneic MSCs in several immunocompromised diseases.…”