CD4+ T-regulatory cells: toward therapy for human diseases

T-regulatory cells (Tregs) have a fundamental role in theestablishment and maintenance of peripheral tolerance. There is nowcompelling evidence that deficits in the numbers and/or function ofdifferent types of Tregs can lead to autoimmunity, allergy, and graftrejection, whereas an over-abundance of Tregs can inhibit anti-tumorand anti-pathogen immunity. Experimental models in mice have demonstratedthat manipulating the numbers and/or function of Tregs candecrease pathology in a wide range of contexts, including transplantation,autoimmunity, and cancer, and it is widely assumed that similar approacheswill be possible in humans. Research into how Tregs can bemanipulated therapeutically in humans is most advanced for two maintypes of CD41 Tregs: forkhead box protein 3 (FOXP3)1 Tregs andinterleukin-10-producing type 1 Tregs (Tr1 cells). The aim of this reviewis to highlight current information on the characteristics of humanFOXP31 Tregs and Tr1 cells that make them an attractive therapeutictarget. We discuss the progress and limitations that must be overcome todevelop methods to enhance Tregs in vivo, expand or induce them in vitro foradoptive transfer, and/or inhibit their function in vivo. Although manytechnical and theoretical challenges remain, the next decade will see thefirst clinical trials testing whether Treg-based therapies are effective inhumans.