@article {542591, title = {PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells.}, journal = {Proc Natl Acad Sci U S A}, volume = {101}, number = {29}, year = {2004}, month = {2004 Jul 20}, pages = {10691-6}, abstract = {Both positive and negative regulatory roles have been suggested for the B7 family member PD-L1(B7-H1). PD-L1 is expressed on antigen-presenting cells (APCs), activated T cells, and a variety of tissues, but the functional significance of PD-L1 on each cell type is not yet clear. To dissect the functions of PD-L1 in vivo, we generated PD-L1-deficient (PD-L1(-/-)) mice. CD4(+) and CD8(+) T cell responses were markedly enhanced in PD-L1(-/-) mice compared with wild-type mice in vitro and in vivo. PD-L1(-/-) dendritic cells stimulated greater wild-type CD4(+) T cell responses than wild-type dendritic cells, and PD-L1(-/-) CD4(+) T cells produced more cytokines than wild-type CD4(+) T cells in vitro, demonstrating an inhibitory role for PD-L1 on APCs and T cells. In vivo CD8(+) T cell responses also were significantly enhanced, indicating that PD-L1 has a role in limiting the expansion or survival of CD8(+) T cells. Studies using the myelin oligodendrocyte model of experimental autoimmune encephalomyelitis showed that PD-L1 on T cells and in host tissues limits responses of self-reactive CD4(+) T cells in vivo. PD-L1 deficiency converted the 129S4/SvJae strain from a resistant to experimental autoimmune encephalomyelitis-susceptible strain. Transfer of encephalitogenic T cells from wild-type mice into PD-L1(-/-) recipients led to exacerbated disease. Disease was even more severe in PD-L1(-/-) recipients of PD-L1(-/-) T cells. These results demonstrate that PD-L1 on T cells, APCs, and host tissue inhibits na{\"\i}ve and effector T cell responses and plays a critical role in T cell tolerance.}, keywords = {Adoptive Transfer, Animals, Antigen-Presenting Cells, Antigens, CD274, Antigens, CD80, Blood Proteins, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Encephalomyelitis, Autoimmune, Experimental, Immune Tolerance, Immunization, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Knockout, Peptides, Phenotype}, issn = {0027-8424}, doi = {10.1073/pnas.0307252101}, author = {Latchman, Yvette E and Liang, Spencer C and Wu, Yin and Chernova, Tatyana and Sobel, Raymond A and Klemm, Martina and Kuchroo, Vijay K and Freeman, Gordon J and Sharpe, Arlene H} }