期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：29
页码：10691-10696
DOI：10.1073/pnas.0307252101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 naive and effector T cell responses and plays a critical role in T cell tolerance.
