Figure 4.

Costimulation and coinhibition. The binding of CD28 or CTLA-4 receptors on T cells by B7.1 and B7.2 ligands on antigen-presenting cells (APCs) can lead to either costimulation or coinhibition depending upon the precise expression patterns of the receptors and ligands and on the state of activation of the two cells. (a) CD28 is expressed on resting T cells and can be engaged by either B7.1 or B7.2 on APCs. Current models favor preferential engagement by B7.2, leading to activation of resting T cells. This costimulation leads in the T cell to increased production of growth factors, such as interleukin-2 (IL-2) and increased cell-survival signals, such as Bcl-X. Reverse signaling by CD28 engagement of B7.1 (not shown) or B7.2 ligands resulting in production of interleukin-6 (IL-6) by the APC has also been described. (b) CD28 and CTLA-4 are both expressed on activated T cells, and both receptors on T cells can be engaged by B7.1 or B7.2 on APCs. Current models favor preferential engagement of CTLA-4 by B7.1, resulting in attenuation of T-cell activation. Reverse signaling by CTLA-4 engagement of B7.1 or B7.2 (not shown) ligands resulting in production of indoleamine 2, 3-dioxygenase (IDO) and a reduction in tryptophan levels in the APC has also been described.