Negative costimulatory molecules: the proximal of regulatory T cells?

Regulatory T cells (Tregs) are a central mechanism of immune regulation. It is well known that their regulatory effect is antigen-specific and depends on cell-cell contact. In addition, some immunological phenomenon such as linked suppression and iDC-induced tolerance are related with Tregs. But the surface markers, which reliably distinguish Treg from other T cell populations, and the regulatory mechanism still remain to be further revealed. Negative costimulatory molecule (NCM) family is one natural intrinsic mechanism that delivers the negative signal into cytoplasma to modulate immunoresponse and its expression can be induced not only on the immune cells but also on the parenchymal cells. Based on the present knowledge, we hypothesize NCMs are the specific surface markers to define Tregs. Tregs are one kind of activated T cells with high expression of NCM receptor and have the capability to induce NCM ligands expression on the membrane of APCs and the target cells of the activated cells. The NCM receptor-ligand complexes deliver negative signal into lymphocytes to regulate the immune response. This hypothesis remains to be fully elucidated.