Mesenchymal Stem Cells Use HLA-G to Suppress T Cells

Cedex, France -

The fact that mesenchymal stem cells are immune suppressive is established. This is one of the reasons why companies such as Osiris are trying to get them approved as an "off the shelf" product that does not require matching.

Several mechanisms are known by which mesenchymal stem cells suppress the immune response, including expression of Fas ligand, activation of the tryptophan catabolizing enzyme indolamine 2,3 deoxygenase, production of IL-10, as well as TGF-beta. Additionally, mesenchymal stem cells are known to induce generation of T suppressor cells.

Now any immunologist looking at this situation would wonder...what other immune suppressive things would mesenchymal stem cells express?

Well, I for one would look at HLA-G.

HLA-G is a nonclassical major histocompatibility complex class I protein that is expressed on tumors, as well as at the fetal-maternal interface, where it acts as a regulator of immune responses by binding ligands such as the Ig-like transcript 2 (ILT2) and ILT4.

In a recent paper (Nasef et al. Immunosuppressive Effects of Mesenchymal Stem Cells: Involvement of HLA-G. Transplantation. 2007 Jul 27;84(2):231-7) expression of HLA-G was assessed on mesenchymal cells obtained from human bone marrow.

HLA-G transcript and protein were found specifically expressed on human bone marrow derived mesenchymal stem cells.

Functionally, HLA-G plays an important role in the ability of mesenchymal stem cells to inhibit mixed lymphocyte reaction. This was demonstrated by experiments showing that addition of anti-HLA-G antibodies abrogated ability of mesenchymal stem cells to suppress mixed lymphocyte reaction.