Toll-like receptors and immune regulation: their direct and indirect modulation on regulatory CD4+ CD25+ T cells.

Regulatory CD4(+) CD25(+) T (Treg) cells with the ability to suppress host immune responses against self- or non-self antigens play important roles in the processes of autoimmunity, transplant rejection, infectious diseases and cancers. The proper regulation of CD4(+) CD25(+) Treg cells is thus critical for optimal immune responses. Toll-like receptor (TLR)-mediated recognition of specific structures of invading pathogens initiates innate as well as adaptive immune responses via antigen-presenting cells (APCs). Interestingly, new evidence suggests that TLR signalling may directly or indirectly regulate the immunosuppressive function of CD4(+) CD25(+) Treg cells in immune responses. TLR signalling may shift the balance between CD4(+) T-helper cells and Treg cells, and subsequently influence the outcome of the immune response. This immunomodulation pathway may therefore have potential applications in the treatment of graft rejection, autoimmune diseases, infection diseases and cancers.