Biological functions of regulatory T cells.

The subpopulation of CD4(+) T lymphocytes that co-express the transcription factor Foxp3 plays a unique role as regulatory T lymphocytes (Tregs) that modulate many aspects of the immune response. Multiple mechanisms have been proposed for the suppressor function of CD4(+)Foxp3(+) T cells based on in vitro studies, but much less is known about how Tregs suppress immune responses in vivo. Both polyclonal Tregs and antigen-specific Tregs are capable of exerting potent suppressive effects in vivo, and it is likely that they mediate their biologic functions using different mechanisms. Antigen-specific Tregs primarily target dendritic cells and inhibit dendritic cell functions including the expression of costimulatory molecules and the presentation of antigen early during the generation of the immune response. The end result is a complete inhibition of both the expansion and the differentiation of T effector cells. Polyclonal Tregs also act on dendritic cells, but at a later phase, and do not inhibit expansion of T effector cells, but appear to modulate differentiation and cell trafficking. The cell surface molecules involved in the interaction of Tregs with dendritic cells, as well as the biochemical pathways modified by this interaction remain to be fully elucidated. A complete understand of the biological functions of Tregs in vivo should facilitate the development of pharmacologic and biologic agents that can be used to modulate Treg function in a therapeutic setting.