New T regulatory marker found: Folate Receptor 4

Kyoto, Japan -

One of the exciting uses of stem cells is suppression of inflammatory reactions. In other words, various types of stem cells, such as mesenchymal stem cells, are known to possess membrane-bound molecules that inhibit T cell activation, or soluble products such as HLA-G5 which also inhibits T cell activation. The immune system can be regulated by stem cells through another means besides inhibition, which is stimulation of immune regulatory cells. One such cell is the T regulatory cell. This cell population has the ability to antigen-specifically be stimulated, but in many cases antigen-nonspecifically inhibit activation of other T cells.

T regulatory cells are a subject of much investigation since they could potentially be useful for silencing pathological immune responses in situations such as autoimmunity or organ transplant rejection.

One of the problems in T regulatory cell research is that distinct markers for these cells are still somewhat unclear. The conventional phenotype that people ascribe to T regulatory cells is the CD4+ CD25+ phenotype. Unfortunately, CD25 is also found on activated T cells. To circumvent this, the expression of FoxP3, a transcription factor intracellularly residing, has been added to the list of markers.

In a recent study (Yamaguchi et al. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. 2007 Jul;27(1):145-59) a new marker was identified that is preferentially expressed on "natural" T regulatory cells. By the way, "natural" T regulatory cells means cells that originate from the thymus, whereas "adaptive" T regulatory cells originate in the periphery.

The investigators found that cells expressing folate receptor 4 were capable of suppressing allogeneic immune responses, and that giving animals antibodies to folate receptor 4 led to upregulation of anti-tumor immunity, and in some situations stimulation of autoimmunity.

It will be interesting to find out what the physiological role of folate receptor 4 is on natural T regulatory cells.