Mesenchymal Stem Cells Inhibit Gamma Delta T Cell Proliferation

Toulouse, France -

We have previously discussed that mesenchymal stem cells inhibit T cell proliferation, activate suppressor T cells, inhibit homeostatic T cell expansion and can be used as universal donors in some situations due to their hypoimmunogenic activies as well as ability to suppress alloreactivity.

In the current paper (Martinet et al. A regulatory cross-talk between Vgamma9Vdelta2 T lymphocytes and mesenchymal stem cells. European Journal of Immunology 2009 Feb 5) the effects of mesenchymal stem cells on a type of gamma delta T cells are investigated.

Gamma Delta T cells are known to recognize non-conventional antigens such as phosphopeptides and lipids.  These cells are usually involved in innate immune responses and guard the body against cancer and certain bacteria.

The investigators isolated gamma delta T cells by purifying for the T cell receptor V gamma 9 V delta 2, and stimulated the cells with either artificial phosphoantigen or lymphoma cell lines.  When the gamma delta T cells were activated in the presence of mesenchymal stem cells suppression of proliferation, inhibited killing activity and reduction in cytokine production was observed. 

Inhibitory effects mediated by mesenchymal stem cells seemed to be associated with expression of cyclo-oxygenase II on the mesenchymal stem cells which produced PGE-2.  Expression of COX-2 and PGE-2 occurred as a result of TNF and interferon produced by the gamma delta T cells during activation.  Further, gamma delta T cells were inhibited by expression of the inhibitory receptors EP2 and EP4.

Overall these data suggest that mesenchymal stem cells inhibit not only adaptive immunity associated, conventional T cells, but also the more "innate" T cells, the gamma delta cells.

Now why would mesenchymal stem cells want to inhibit natural responses that would conceptually be protective against neoplasia?  Maybe it is because the mesenchymal stem cells themselves have other anticancer activities they mediate such as secretion of Dkk-1?