Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases

Abstract

A lack of regulatory T (T(Reg)) cells that express CD4, CD25 and forkhead box P3 (FOXP3) results in severe autoimmunity in both mice and humans. Since the discovery of T(Reg) cells, there has been intense investigation aimed at determining how they protect an organism from autoimmunity and whether defects in their number or function contribute to the development of autoimmunity in model systems. The next phase of investigation - that is, to define the role that defects in T(Reg) cells have in human autoimmunity - is now underway. This Review summarizes our progress so far towards understanding the role of CD4(+)CD25(+)FOXP3(+) T(Reg) cells in human autoimmune diseases and the impact that this knowledge might have on the diagnosis and treatment of these diseases.

Conflict of interest statement

Competing interests statement

The author declares no competing financial interests.

Figures

Figure 1. Causes of impaired TReg cell-mediated suppression in autoimmunity

Autoimmunity can result from a loss of regulation of autoreactive T cells. Failures of regulatory T (TReg) cell-mediated regulation include: inadequate numbers of TReg cells owing to their inadequate development, proliferation or survival; defects in TReg cell function that is intrinsic to TReg cells; and resistance of pathogenic effector T cells to suppression by TReg cells owing to factors that are intrinsic to the effector cells or factors that are present in the inflammatory milieu and that support effector T cell resistance. DC, dendritic cell; IL, interleukin; TGFβ, transforming growth factor-β; TH17, T helper 17.