Brief report--human embryonic stem cell-derived mesenchymal progenitors possess strong immunosuppressive effects toward natural killer cells as well as T lymphocytes.
The derivation of mesenchymal progenitors from human embryonic stem cells (hESCs) has recently been reported. We studied the immune characteristics of these hESC-derived mesenchymal progenitors (EMPs) and their interactions with T lymphocytes and natural killer cells (NKs), two populations of lymphocytes with important roles in transplantation immunology. EMPs express a number of bone marrow mesenchymal stromal cell (BMMSC) markers, as well as the hESC marker SSEA-4. Immunologically, EMPs do not express HLA-DR or costimulatory molecules. On the other hand, HLA-G, a nonclassic MHC I protein involved in mediating maternal-fetal tolerance, can be found on the surface of EMPs, and its expression is increased after interferon-gamma stimulation. EMPs can suppress CD4(+) or CD8(+) lymphocyte proliferation, similar to BMMSCs. However, EMPs are more resistant to NK-mediated lysis than BMMSCs and can suppress the cytotoxic effects of activated NKs, as well as downregulating the NK-activating receptors NKp30 and NKp46. With their broad immunosuppressive properties, EMPs may represent a new potential cell source for therapeutic use.
Yen
B Linju
BL
Regenerative Medicine Research Group, Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan.
Chang
Chan Jung
CJ
Liu
Ko-Jiunn
KJ
Chen
Yao Chang
YC
Hu
Hsin-I
HI
Bai
Chi-Huey
CH
Yen
Men-Luh
ML
D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019002:CD56 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D007371:Interferon-gamma