Disease relevance of PDCD1LG2

• Second, we assessed the therapeutic potential of neutralizing anti-B7-H1 and/or B7-DC mAbs using this colitis model [1].
• These results suggest that epithelial B7-H1 and B7-DC play a role in virus-associated immune responses in the airways [2].
• In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival [3].
• In this study, we investigated the expression of PD-L1 and PD-L2 in human esophageal cancer to define their clinical significance in patients' prognosis after surgery [4].
• Expression of programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulator ligand on human respiratory tract epithelial cells and regulation by respiratory syncytial virus and type 1 and 2 cytokines [5].

High impact information on PDCD1LG2

• In addition, the PD-1:PD-L1/PD-L2 pathway plays a critical role in regulating T cell activation and tolerance [6].
• PD-1 has two ligands: PD-1 ligand 1 (PD-L1), which is expressed broadly on hematopoietic and parenchymal cells, including pancreatic islet cells; and PD-L2, which is restricted to macrophages and dendritic cells [7].
• The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines [8].
• B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells [9].
• These properties of B7-DC may account for some of the unique activity of DCs, such as their ability to initiate potent T helper cell type 1 responses [9].

Biological context of PDCD1LG2

• A relatively high concentration of dexamethasone (1 microM) was required to suppress the upregulation of B7-H1 or B7-DC [2].
• EXPERIMENTAL DESIGN: PD-L1 and PD-L2 gene expression was evaluated in 41 esophagectomy patients by real-time quantitative PCR [4].
• The common PD-L2 mRNA (type I) is the splicing product containing all 6 exons [10].
• These results suggest that PD-L2 expression may be controlled by posttranscriptional regulation through alternative splicing, and modulation of PD-L2 isoform expression may influence the outcome of immune response [10].
• This study suggests a relatively minor contribution of PD-1 ligands in DC-driven CD4(+) T cell activation and provides evidence for reverse signaling by PD-L1 and PD-L2 into DC, resulting in a suppressive DC phenotype [11].

Anatomical context of PDCD1LG2

• PD-L2 is a second ligand for PD-1 and inhibits T cell activation [12].
• We investigated the effect of dsRNA on the expression of B7-H1 and B7-DC on airway epithelial cell lines [2].
• Expression of B7-H1 and B7-DC on the airway epithelium is enhanced by double-stranded RNA [2].
• In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells [13].
• Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells [13].

Associations of PDCD1LG2 with chemical compounds

• B7-H1 and B7-DC were constitutively expressed on the cells, and their expression was profoundly upregulated by stimulation with an analog of viral dsRNA, polyinosinic-polycytidylic acid [2].
• Fluticasone treatment (10(-7) M) reduced the baseline expression and inhibited the induction of B7-H1 and B7-DC in BEAS2B cells [14].
• Comparison of their N-terminal sequences, up to residue 45, showed that PD-L1 is identical to PD-L2 [designated the isoleucine (Ile) form from the N-terminal residue] and PD-L3 is identical to PD-L4 [designated the valine (Val) form from the N-terminal residue] and that there are 35 identical residues between the two forms [15].

Regulatory relationships of PDCD1LG2

• Monoclonal antibody blockade of B7-H1 or B7-DC enhanced IFN-gamma expression by purified T cells in co-culture experiments, suggesting that these two B7 homologs inhibit T cell responses at the mucosal surface [14].

Other interactions of PDCD1LG2

• Blocking PD-1 reverted the inhibitory effect of PD-L2, demonstrating involvement of this pathway [16].
• PD-L2 inhibition affected CD4(+) and CD8(+) T cells and was not abrogated by costimulation via CD28 [16].
• Unstimulated cultured KCs expressed both B7-H1 and B7-DC, and their expression was upregulated by proinflammatory cytokines, particularly IFN-gamma [17].
• Anti-CD3 mAb + PD-L2 stimulation also increased the level of SHP-2 associated with the PD-1 receptor [18].
• B7-DC was a strong inhibitor of CD4+T-cell activation, as assessed by increased cytokine (interferon-gamma and interleukin-2) production and enhanced levels of T-cell activation marker CD69 in the presence of its blocking antibody [19].

Analytical, diagnostic and therapeutic context of PDCD1LG2

• CONCLUSIONS: These data suggest that PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with esophageal cancer and provide the rationale for developing novel immunotherapy of targeting PD-1/PD-L pathway [4].
• Blockade of PD-1 or B7-H1, but not B7-DC, led to accelerated corneal allograft rejection [20].
• Adoptive transfer from mice pretreated with intratracheal delivery of alloantigen plus control IgG or anti-PD-L2 mAb prolonged survival of C57BL/10 grafts in secondary CBA recipients (MST, 72 and 56 days, respectively) [21].
• With the exception of PD-L4, the purified RIPs gave a positive reaction when stained for sugars on SDS-PAGE gels and, when analyzed by electrospray mass spectrometry, had M(r) values of 32,715 +/- 1 (PD-L1), 31,542 +/- 1 (PD-L2), 30,356 +/- 1 (PD-L3) and 29,185 +/- 1 Da (PD-L4) [15].

References