The role of CD28 and CTLA-4 in regulatory T cell biology

The profound influence of CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on T-cell immunity has been known for over a decade, yet the precise roles played by these molecules still continue to emerge. Initially viewed as molecules that provide cell-intrinsic costimulatory and inhibitory signals, recent evidence suggests that both CD28 and CTLA-4 are also important in the homeostasis and function of a population of suppressive cells, termed regulatory T cells (Tregs). Here we review the main features of the CD28 and CTLA-4 system and examine how these impact upon Treg biology.