Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes

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.

Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal

“…Molecule of the CD28 family that binds B7-H1 (CD274) and is involved in negative regulation of lymphocytes [50,51]. Molecules involved in cell proliferation: CD25 Inducible IL-2 receptor alpha chain [52].…”

Programmed cell death 1 (PD‐1) and its ligand PD‐L1 are required for allograft tolerance

“…Programmed cell death 1 (PD-1, CD279) is a type 1 transmembrane protein containing an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM) [1], which is induced upon the activation of CD4 and CD8 T cells as well as B, NKT and myeloid cells [2]. PD-1 has two ligands, PD-L1 (also known as B7-H1 or CD274), constitutively expressed by many tissues and upregulated on activation [3], and PD-L2 (also known as B7-DC or CD273), expressed primarily by activated DC and macrophages [4].…”

Preferential contribution of B7‐H1 to programmed death‐1‐mediated regulation of hapten‐specific allergic inflammatory responses

“…PD-1 has two tyrosine residues in its cytoplasmic domain, which form an immunoreceptor tyrosine-based inhibitory motif (ITIM) [6,8] and an immunoreceptor tyrosine-based switch motif (ITSM) [9]. PD-1 is expressed on a subpopulation of thymocytes and on both T and B cells after antigenic stimulation [6, 10,11]. Although PD-1-deficient mice develop autoimmune diseases, such as lupus-like glomerulonephritis and dilated cardiomyopathy [8,12], these mice display markedly different phenotypes as compared with CTLA-4-deficient mice [13][14][15], suggesting a role for PD-1 distinct from that for CTLA-4.…”