Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes

  title={Mesenchymal stem cells fail to trigger effector functions of cytotoxic T lymphocytes},
  author={Ida Rasmusson and Michael Uhlin and Katarina Le Blanc and Victor G. Levitsky},
  journal={Journal of Leukocyte Biology},
Mesenchymal stem cells (MSCs), isolated from adult human bone marrow, have immunomodulatory properties. The functional outcomes of MSCs–CTL interactions remain poorly characterized. In this study, we demonstrate that MSCs remain resistant to CTL lysis, even after pulsing with the specific synthetic peptide at high concentrations, in spite of surface expression of the relevant MHC class I allele. MSCs were also much less sensitive to lysis by an allo‐specific CTL clone as compared with HLA… 

Immunogenicity of Human Mesenchymal Stem Cells in HLA‐Class I‐Restricted T‐Cell Responses Against Viral or Tumor‐Associated Antigens

Human MSC can process and present HLA class I‐restricted viral or tumor antigens to specific CTL with a limited efficiency, likely because of some defects in APM components, but are protected from CTL‐mediated lysis through a mechanism that is partly sHLA‐G‐dependent.

Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses.

MSCs have little effect on T-cell responses to EBV and CMV, which contrasts to their strong immunosuppressive effects on alloreactive T cells, which 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.

Clinical‐Grade Human Multipotent Adult Progenitor Cells Block CD8+ Cytotoxic T Lymphocytes

This study confirms that these clinical‐grade MAPCs are an immune‐modulating population that inhibits CTL activation and effector responses and are, consequently, a highly valuable cell population for adoptive immunosuppressive therapy in diseases where damage is induced by CTLs.

Mesenchymal Stromal Cells Protect Endothelial Cells from Cytotoxic T Lymphocyte‐Induced Lysis

The results support the use of MSC as an adjuvant cellular therapeutic in transplant medicine, alone or in conjunction with EC protective agents such as defibrotide.

Mesenchymal stromal cells inhibit proliferation of virus-specific CD8+ T cells

It is confirmed that MSCs strongly inhibited proliferation of CD8+ T cells in a mixed lymphocyte reaction, and also suppressed proliferation of T cells specifically recognizing cytomegalovirus (CMV) and influenza virus.

Long-Lasting Inhibitory Effects of Fetal Liver Mesenchymal Stem Cells on T-Lymphocyte Proliferation

Fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection because of their longer lasting in vitro immunosuppressive properties and their more efficient induction of IL-10 production and T cell apoptosis.

b TGF-Role of Mesenchymal Stem Cell-Derived Cancer Cells through Regulatory T Cells: Mesenchymal Stem Cells Protect Breast

Two studies show an MSC-mediated increase in T regs in cocultures of PBMCs and BCCs and demonstrate immune protection by MSCs to BCCs, which has implications for treatment of breast cancer with chemo-therapy.

Mesenchymal stem cell effects on T-cell effector pathways

It is concluded that MSCs have the potential to directly or indirectly inhibit disease-associated Th1, Th2, and Th17 cells as well as cytotoxic T lymphocytes but that many key questions regarding the potency, specificity, mechanistic basis, and predictable therapeutic value of these modulatory effects remain unanswered.

Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways.

Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy.

Mesenchymal Stem Cells Protect Breast Cancer Cells through Regulatory T Cells: Role of Mesenchymal Stem Cell-Derived TGF-β

Two studies show an MSC-mediated increase in Tregs in cocultures of PBMCs and BCCs, and the reduction in immune cell proliferation and recruitment mediated by MSCs has implications for treatment of breast cancer with chemotherapy.



Human mesenchymal stem cells modulate allogeneic immune cell responses.

Insight is offered into the interactions between allogeneic MSCs and immune cells and mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation.

Human mesenchymal stem cells suppress induction of cytotoxic response to alloantigens.

It is demonstrated that MSC, which can be recognized as targets by pre-activated alloreactive CTLs, may be able to suppress differentiation of CTL precursors into CTL effectors through secretion of suppressive factors.

T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression.

It is concluded that MSCs can initiate activation of alloreactive T cells, but do not elicit T cell proliferative responses due to active suppressive mechanisms.

Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells.

MSC-mediated inhibition induces an unresponsive T-cell profile that is fully consistent with that observed in division arrest anergy.

Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype.

The results strongly suggest that MSC-mediated inhibition of alloantigen-induced DC1 differentiation and preferential activation of CD4+ CD25+ T-cell subsets with presumed regulatory activity represent important mechanisms contributing to the immunosuppressive activity of MSC.

Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation

Human MSC fail to stimulate allogeneic PBMC or T-cell proliferation in mixed cell cultures, and actively inhibit T- cell proliferation, suggesting that allogeneIC MSC transplantation might be accomplished without the need for significant host immunosuppression.

Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness.

The data support an immunoregulatory mechanism wherein hMSCs inhibit T cells indirectly by contact-dependent induction of regulatory APCs with T-cell-suppressive properties and may reveal a physiologic phenomenon whereby the development of a distinct APC population is regulated by the tissue's cellular microenvironment.

Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide.

It is suggested that MSCs physically hinder T cells from the contact with APCs in a noncognate fashion and inhibit naive and memory T-cell responses to their cognate antigens.

Veto-Like Activity of Mesenchymal Stem Cells: Functional Discrimination Between Cellular Responses to Alloantigens and Recall Antigens1

It was shown that MSC could blunt the cytotoxic effects of allogeneic-induced effectors to mitogen-activated targets, and exerted veto-like activity, but caused no effect on responses to recall Ags.