Upregulation of PD-1 and its ligands PD-L1 and PD-L2 is observed during acute virus infection and after infection with persistent viruses including important human pathogens such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV).
Expression of programmed cell death protein 1 and T-cell immunoglobulin- and mucin-domain-containing molecule-3 on peripheral blood CD4+CD8+ double positive T cells in patients with chronic hepatitis C virus infection and in subjects who spontaneously cleared the virus.
Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
In chronic viral hepatitis, the extended upregulations of PD-1 and CTLA-4 are associated with T cell exhaustion and persistent viral infection, suggesting positive correlations between expression of immune inhibitory factors and the chronicity of viral disease.
Programmed cell death-1/programmed cell death-1 ligand 1 (PD-1/PD-L1) inhibitory signal pathway has been verified to be involved in the establishment of persistent viral infections.
Collectively, this study shows that CTLs adapt to persistent infection through a positive feedback pathway (PD-1?FoxO1?PD-1) that functions to both desensitize virus-specific CTLs to antigen and support their survival during chronic viral infection.
Cooperation or interaction of programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) molecules is more relevant than either molecule alone to immune dysfunction in chronic viral infection and cancers.
Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV).
Our data provide the first evidence that PDCD1 polymorphisms is a genetic factor in pathogenesis of chronic viral infection and reveal the functional significance of the P7209 SNP of the PDCD1.