Journal ArticleDOI
Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes
Yasutoshi Agata,Akemi Kawasaki,Hiroyuki Nishimura,Yasumasa Ishida,Takeshi Tsubata,Hideo Yagita,Tasuku Honjo +6 more
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TLDR
The results suggest that the expression of thePD-1 antigen is tightly regulated and induced by signal transduction through the antigen receptor and do not exclude the possibility that the PD- 1 antigen may play a role in clonal selection of lymphocytes although PD-1 expression is not required for the common pathway of apoptosis.Abstract:
A mAb J43 has been produced against the product of the mouse PD-1 gene, a member of the Ig gene superfamily, which was previously isolated from an apoptosis-induced T cell hybridoma (2B4.11) by using subtractive hybridization. Analyses by flow cytometry and immunoprecipitation using the J43 mAb revealed that the PD-1 gene product is a 50-55 kDa membrane protein expressed on the cell surface of several PD-1 cDNA transfectants and 2B4.11 cells. Since the molecular weight calculated from the amino acid sequence is 29, 310, the PD-1 protein appears to be heavily glycosylated. Normal murine lymphoid tissues such as thymus, spleen, lymph node and bone marrow contained very small numbers of PD-1(+) cells. However, a significant PD-1(+) population appeared in the thymocytes as well as T cells in spleen and lymph nodes by the in vivo anti-CD3 mAb treatment. Furthermore, the PD-1 antigen expression was strongly induced in distinct subsets of thymocytes and spleen T cells by in vitro stimulation with either anti-CD3 mAb or concanavalin A (Con A) which could lead T cells to both activation and cell death. Similarly, PD-1 expression was induced on spleen B cells by in vitro stimulation with anti-IgM antibody. By contrast, PD-1 was not significantly expressed on lymphocytes by treatment with growth factor deprivation, dexamethasone or lipopolysaccharide. These results suggest that the expression of the PD-1 antigen is tightly regulated and induced by signal transduction through the antigen receptor and do not exclude the possibility that the PD-1 antigen may play a role in clonal selection of lymphocytes although PD-1 expression is not required for the common pathway of apoptosis.read more
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Journal ArticleDOI
Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
Gordon J. Freeman,Andrew J. Long,Yoshiko Iwai,Karen Bourque,Tatyana Chernova,Hiroyuki Nishimura,Lori Fitz,Nelly Malenkovich,Taku Okazaki,Michael C. Byrne,Heidi F. Horton,Lynette A. Fouser,Laura L. Carter,Vincent Ling,Michael R Bowman,Beatriz M. Carreno,Mary Collins,Clive Wood,Tasuku Honjo +18 more
TL;DR: It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.
Journal ArticleDOI
PD-1 and its ligands in tolerance and immunity
TL;DR: Current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential are discussed and an inhibitory bidirectional interaction between PD-L1 and B7-1 is discovered, revealing new ways the B7:CD28 family regulates T cell activation and tolerance.
Journal ArticleDOI
Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion
Haidong Dong,Scott E. Strome,Diva R. Salomao,Hideto Tamura,Fumiya Hirano,Dallas B. Flies,Patrick C. Roche,Jun Lu,Gefeng Zhu,Koji Tamada,Vanda A. Lennon,Esteban Celis,Lieping Chen +12 more
TL;DR: It is reported here that, except for cells of the macrophage lineage, normal human tissues do not express B7-H1 and the findings have implications for the design of T cell–based cancer immunotherapy.
Journal ArticleDOI
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Yvette Latchman,Clive Wood,Tatyana Chernova,Divya Chaudhary,Madhuri Borde,Irene Chernova,Yoshiko Iwai,Andrew J. Long,Julia A. Brown,Raquel A. Nunes,Edward A. Greenfield,Karen Bourque,Vassiliki A. Boussiotis,Laura L. Carter,Beatriz M. Carreno,Nelly Malenkovich,Hiroyuki Nishimura,Taku Okazaki,Tasuku Honjo,Arlene H. Sharpe,Gordon J. Freeman +20 more
TL;DR: These studies show overlapping functions of PD-L1 andPD-L2 and indicate a key role for the PD- L–PD-1 pathway in regulating T cell responses.
Journal ArticleDOI
Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade
TL;DR: The results suggest that the expression of PD-L1 can serve as a potent mechanism for potentially immunogenic tumors to escape from host immune responses and that blockade of interaction between PD-1 andPD-L may provide a promising strategy for specific tumor immunotherapy.
References
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Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
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