The signal and two-thirds of the immunoglobulin (Ig)-V-like exons of the CD274 antigen (Cd274) gene were replaced with a neomycin resistance cassette, abolishing Cd274 gene expression. Cd274 encodes PD-L1, one of two ligands for PD-1 that is upregulated on antigen presenting cells (APCs), activated T cells, myeloid cells, dendritic cells (DCs). It is also expressed on hematopoietic and parenchymal cells. PD-1 is an inhibitory receptor expressed on activated lymphocytes where it regulates tolerance and autoimmunity by negative regulation of T cell responses. Homozygous PD-L1-/- knock-out mice are viable and fertile. Flow cytometry shows lack of expression of PD-L1 in B cells, T cells, macrophages or DCs. CD4+ and CD8+ T cell responses are enhanced in PD-L1-/- mice compared with wildtype mice in vitro and in vivo. PD-L1-/- DCs stimulate greater wildtype CD4+ T cell responses than wildtype DCs, and PD-L1-/- CD4+ T cells produce more cytokines than wildtype CD4+ T cells in vitro, demonstrating an inhibitory role for PD-L1 on APCs and T cells. In vivo CD8+ T cell responses are also enhanced, indicating that PD-L1 has a role in limiting the expansion or survival of CD8+ T cells.

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PD-L1-/-.B6 mice are C57BL/6-congenic animals carrying the PD-L1- (Cd274-) knock-out mutation. These mice may be useful for studying the role of PD-L1 on T cells, APCs, and host tissue inhibition of naϊve and effector T cell responses and T cell tolerance.