TREG-cell therapies for autoimmune rheumatic diseases

Naturally occurring Foxp3(+)CD25(+)CD4(+) regulatory T (T-REG) cells maintain immunological self-tolerance and prevent a variety of autoimmune diseases, including rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. In animal models of rheumatic disease, autoimmune responses can be controlled by re-establishing the T-cell balance in favour of T-REG cells. Here we discuss three potential strategies for the clinical use of T-REG cells to treat autoimmune rheumatic disease: expansion of self-antigen-specific natural T-REG cells in vivo; propagation of antigen-specific natural T-REG cells ex vivo, by in vitro antigenic stimulation, and subsequent transfer back into the host; or conversion of antigen-specific conventional T cells into T-REG cells in vivo or ex vivo. These strategies require depletion of the effector T cells that mediate autoimmunity before initiating T-REG-cell-based therapies. Immunotherapies that target T-REG cells, and the balance of T-REG cells and autoreactive T cells, are therefore an important modality for the treatment of autoimmune rheumatic disease.