Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes.
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.
Agata
Y
Y
Center for Molecular Biology and Genetics, Faculty of Medicine, Kyoto University, Japan.
Kawasaki
A
A
Nishimura
H
H
Ishida
Y
Y
Tsubata
T
T
Yagita
H
H
Honjo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000737:chemistry; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology*; D011233:Precipitin Tests; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins