Expression of PD-L1 on CD4+CD25+Foxp3+ Regulatory T Cells of Patients with Chronic HBV Infection and Its Correlation with Clinical Parameters

Abstract

Regulatory T cells (Tregs) play a pivotal role in suppressing specific antiviral immune responses during the progression of chronic hepatitis B virus infection (CHB) as well as tumorigenesis. Programmed death-1 ligand-1 (PD-L1) expressed on Tregs can transduce an inhibitory signal into effector T cells through interacting with programmed death-1 (PD-1). However, in CHB patients, the clinical significance of PD-L1 expression on Tregs has not been clearly described. This study investigated the frequency of circulating Tregs and PD-L1 expression on Tregs and analyzed their correlations with clinical parameters. The data show that both the frequency of CD4+CD25+FoxP3+ Tregs and PD-L1 expression on Tregs in the peripheral blood increased significantly in CHB patients when compared with healthy controls. At the same time, it is shown that PD-L1 expression on Tregs was positively correlated with the percentage of Tregs in CHB patients. Moreover, the results demonstrated that both Treg frequency and PD-L1 expression on Tregs positively correlated with the levels of alanine aminotransaminase (ALT) and aspartate aminotransferase (AST), both of which are indicators of the extent of liver injury. Taken together, these findings suggest that PD-L1 on Tregs might contribute to progression of hepatitis B virus infection through mediating the inhibitory function of Tregs. Thereby, blockade of interaction between Treg-expressing PD-L1 and PD-1 on effector T cells may be adopted as a potential therapeutic approach in CHB.

Regulatory T cells and T helper 17 cells in viral infection

“…In patients with HBV, Tregs inhibit HBV‐specific T cell response via a variety of mechanisms. Expression of programmed death‐1 ligand‐1 (PD‐L1) is significantly upregulated on Tregs in chronic hepatitis B (CHB) patients . When binding to its receptor, PD‐L1 could transduce the inhibitory signal into effector T cells, suppress effector T cell response and promote the progress of HBV infection .…”

“…Expression of programmed death‐1 ligand‐1 (PD‐L1) is significantly upregulated on Tregs in chronic hepatitis B (CHB) patients . When binding to its receptor, PD‐L1 could transduce the inhibitory signal into effector T cells, suppress effector T cell response and promote the progress of HBV infection . Additionally, Tregs can secrete interleukin‐35 (IL‐35), a potent immunosuppressive cytokine with the ability to inhibit T cell proliferation and effector function .…”

Stromal PD-L1–Positive Regulatory T cells and PD-1–Positive CD8-Positive T cells Define the Response of Different Subsets of Non–Small Cell Lung Cancer to PD-1/PD-L1 Blockade Immunotherapy

“…The expression of PD-L1 in CD25-positive CD4positive Tregs plays an important role in many diseases and infections, 23,25 and studies have shown that PD-L1 expression in TILs is correlated with objective responses. 26 To elucidate the role of PD-L1-positive CD25positive CD4-positive Tregs and PD-1 TILs in NSCLC, we first investigated the expression of PD-L1 in CD25positive CD4-positive Tregs from 42 large (diameter !10 mm 3 ) fresh NSCLC tumor specimens obtained from surgical procedures.…”

Chronic hepatitis B surface antigen seroclearance‐related immune factors

“…It was reported that PD‐1hiCD127low‐exhausted CD8+ lymphocytes can make pAAV/core‐null mutants and may affect the removal of the surface antigen . There is increasing evidence indicating a role for PD‐1 in maintaining HBV infection . However, the relationship between HBsAg and PD‐1 has not yet been clarified.…”

“…102 There is increasing evidence indicating a role for PD-1 in maintaining HBV infection. 102,104,105 However, the relationship between HBsAg and PD-1 has not yet been clarified.…”