Roles of LAG3 and EGR2 in regulatory T cells.

Regulatory T cells (Tregs) participate in the maintenance of tolerance to self-antigens and suppressive control of excessive immune responses to exogenous antigens. A lack or dysfunction of these cells is responsible for the pathogenesis and development of many autoimmune diseases. It is well known that CD4 Tregs play a major role in controlling immune responses and can be classified into two main populations: thymus-derived naturally occurring Tregs (nTregs) and induced Tregs (iTregs) generated from CD4(+)CD25(-) precursors in the peripheral lymphoid organs. The most extensively studied Tregs are the nTregs, which express the interleukin 2 (IL-2) receptor CD25 and the transcription factor Forkhead box P3 (Foxp3). On the other hand, iTregs contain multiple heterogeneous subsets, including interleukin (IL)-10-producing CD4 type I Tregs (Tr1 cells) and transforming growth factor -β-producing Th3 cells, and so on. However, the extent of the contribution of iTregs to immunoregulation in normal animals has been difficult to evaluate because of the lack of suitable cell surface markers. It has been found recently that IL-10-secreting iTregs can be delineated as CD4(+)CD25(-)Foxp3(-) T cells that characteristically express both the lymphocyte activation gene-3 (LAG3) and the early growth response gene-2 (EGR2). In this review, opinions about the roles of LAG3 and EGR2 in Tregs are presented.