B7-H1 expression on old CD8⁺ T cells negatively regulates the activation of immune responses in aged animals

T cell responses are compromised in the elderly. The B7-CD28 family receptors are critical in the regulation of immune responses. We evaluated whether the B7-family and CD28-family receptors were differentially expressed in dendritic cells, macrophages, and CD4⁺ and CD8⁺ T cells from young and old mice, which could contribute to the immune dysfunction in the old. Although most of the receptors were equally expressed in all cells, >85% of the old naive CD8⁺ T cells expressed B7-H1 compared with 25% in the young. Considering that B7-H1 negatively regulates immune responses, we hypothesized that expression of B7-H1 would downregulate the function of old CD8⁺ T cells. Old CD8⁺ T cells showed reduced ability to proliferate, but blockade of B7-H1 restored the proliferative capacity of old CD8⁺ T cells to a level similar to young CD8⁺ T cells. In vivo blockade of B7-H1 restored antitumor responses against the B7-H1 ^- BM-185-enhanced GFP tumor, such that old animals responded with the same efficiency as young mice. Our data also indicate that old CD8⁺ T cells express lower levels of TCR compared with young CD8⁺ T cells. However, following antigenic stimulation in the presence of B7-H1 blockade, the levels of TCR expression were restored in old CD8⁺ T cells, which correlated with stronger T cell activation. These studies demonstrated that expression of B7-H1 in old CD8⁺ T cells impairs the proper activation of these cells and that blockade of B7-H1 could be critical to optimally stimulate a CD8 T cell response in the old.