Suppression by T regulatory (T_reg) cells is essential for the induction of peripheral tolerance. Several types of CD4⁺ T_reg cells have been described in a number of systems. Although the precise mechanisms which mediate T_reg cells effector activity remain to be defined, it is well established that they can suppress immune responses via cell–cell interactions and/or the production of interleukin (IL)10 and transforming growth factor (TGF)β. Type 1 T regulatory (T_reg1) cells are defined by their ability to produce high levels of IL10 and TGFβ, and these cytokines mediate their ability to suppress pathological immune responses in the settings of transplantation, allergy, and autoimmune diseases. T_reg1 cell activity is not necessarily beneficial, and they can also suppress immune responses to antigens from tumours and pathogens. The differentiation of T_reg1 cells in vivo is likely controlled by certain dendritic cells that promote IL10 production and may express tolerogenic co‐stimulatory molecules. Another subset of CD4⁺ T_reg cells is defined by constitutive expression of CD25. Naturally occurring human CD4⁺CD25⁺ T_reg cells are distinct from T_reg1 cells. Suppressive CD4⁺CD25⁺ T cell clones do not synthesize IL10 but produce TGFβ which contributes to the suppression of proliferation mediated by these cells. However, CD4⁺CD25⁺ T_reg cells may be involved in the process inducing the differentiation of T_reg1 cells.

In conclusions, many questions on the basic biology of T_reg cells remain to be answered, but the development of therapeutic strategies designed to harness their immunoregulatory effects can already be envisaged.