Essential for Their Survival B7-H1 Expressed by Activated CD8 T Cells Is

An immunoinhibitory role of B7 homologue 1 (B7-H1) expressed by non-T cells has been established; however, the function of B7-H1 expressed by T cells is not clear. Peak expression of B7-H1 on Ag-primed CD8 T cells was observed during the contraction phase of an immune response. Unexpectedly, B7-H1 blockade at this stage reduced the numbers of effector CD8 T cells, suggesting B7-H1 blocking Ab may disturb an unknown function of B7-H1 expressed by CD8 T cells. To exclusively examine the role of B7-H1 expressed by T cells, we introduced B7-H1 deficiency into TCR transgenic (OT-1) mice. Naive B7-H1–deficient CD8 T cells proliferated normally following Ag stimulation; however, once activated, they underwent more robust contraction in vivo and more apoptosis in vitro. In addition, B7-H1–deficient CD8 T cells were more sensitive to Ca-dependent and Fas ligand-dependent killing by cytotoxic T lymphocytes. Activation-induced Bcl-x L expression was lower in activated B7-H1–deficient CD8 T cells, whereas Bcl-2 and Bim expression were comparable to the wild type. Transfer of effector B7-H1–deficient CD8 T cells failed to suppress tumor growth in vivo. Thus, upregulation of B7-H1 on primed T cells helps effector T cells survive the contraction phase and consequently generate optimal protective immunity. B 7 homologue 1 (B7-H1) is an immunoregulatory molecule in the B7 family. We first described B7-H1 in 1998 (1) and identified its expression in human cancer cells in 2002 (2). Since then, B7-H1 has been reported to be aberrantly expressed by many human cancer cells, and high B7-H1 expression has been correlated with poor prognosis in several human cancers (3). Thus, B7-H1 blockade has been proposed as a means of countering the immunosuppressive effects of tumors to improve tumor immunotherapy (4–7). However, the drive to exploit B7-H1 as a clinical immune target has outpaced any comprehensive understanding of B7-H1 function. B7-H1 is expressed by several cell types, including T cells. Its constitutive expression is primarily restricted to cells of myeloid lineage, such as macrophages and dendritic cells in both mice and humans (1, 2, 8). In other cell types such as lymphoid lineage cells, endothelial, and epithelial cells, B7-H1 expression can be either induced or upregulated by IFN-g and TNF-a (7). Naive murine T cells constitutively express low levels of B7-H1, whereas naive human T cells do not, and both murine and human T cells express markedly increased levels of B7-H1 after activation (1, 8, 9). In contrast to accumulating …