Correlation between low tapasin expression and impaired CD8+ T-cell function in patients with chronic hepatitis B

Abstract

Recent studies have demonstrated that chronic hepatitis B virus (HBV) infection is associated with reduced antigen‑presenting capacity and insufficient cytotoxic T lymphocyte (CTL) production. The molecular chaperone tapasin mediates binding of the transporter associated with antigen processing (TAP), and has an important role in endogenous antigen processing and presentation, and the induction of specific CTL responses. The present study aimed to determine whether tapasin is associated with chronic HBV (CHB) infection. The mRNA expression levels of tapasin were detected in peripheral blood mononuclear cells from 27 patients with CHB, 20 patients with acute HBV (AHB) and 26 healthy controls by reverse transcription‑quantitative polymerase chain reaction. In addition, CD8+ T immune responses were evaluated in all groups, and the correlation between tapasin expression and CD8+ responses was analyzed. The results demonstrated that the mRNA expression levels of tapasin were significantly downregulated in patients with CHB compared with in healthy controls and patients with AHB. Furthermore, the apoptotic rate of CD8+ T cells was increased in patients with CHB compared with in the other two groups. The percentage of interferon (IFN)‑γ+CD8+ T cells was reduced in patients with CHB compared with in patients with AHB and healthy controls, and serum cytokine levels (IFN‑γ, interleukin‑2 and tumor necrosis factor‑α) were generally low in patients with CHB. Furthermore, the mRNA expression levels of tapasin were positively correlated with IFN‑γ production by CD8+ T cells, and were inversely correlated with the apoptotic ratio of CD8+ T cells. These results indicate that decreased expression of tapasin may be closely associated with CHB, and suggest an important role for tapasin in the pathogenesis of CHB.

Maternal pre-pregnancy obesity, offspring cord blood DNA methylation, and offspring cardiometabolic health in early childhood: an epigenome-wide association study

“…While mechanisms linking maternal obesity to sex-specific epigenetic response are still unknown, higher methylation levels of TAPBP such as those found in our study might decrease tapasin via decreased transcriptional activity, leading to impaired immune responses in offspring. Decreased tapasin has been shown to lower CD8 + T-cell responses in vitro [32][33][34][35]. Indeed, tapasin has also been associated with the autoimmune disease rheumatoid arthritis [36][37][38], and like obesity, this condition is also associated with chronic inflammation.…”

Exosomes loading Tapasin enhance T cell immune response by autophagy to inhibit HBV replication

“…Therefore, the decrease of TPN expression is closely related to CHB and involved in the development and progression of CHB. 18 In our previous study, modification of TPN on intracellular antigen peptides could mediate cytokines production and CTL activity to inhibit HBV replication. 19 Exosomes from mDCs have been showed the exciting immune regulation function and potential use as vaccine against cancer and pathogen.…”

“…Compared with healthy controls and acute hepatitis B (AHB) patients, the mRNA expression of TPN in CHB patients was significantly reduced, and the CD8 + T cells apoptosis rate was increased. Therefore, the decrease of TPN expression is closely related to CHB and involved in the development and progression of CHB 18 . In our previous study, modification of TPN on intracellular antigen peptides could mediate cytokines production and CTL activity to inhibit HBV replication 19 …”

Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis

“…Transporter associated with antigen processing (TAP)-binding protein (TAPBP), encoding tapasin involved in class I antigen processing, is an important component of the major histocompatibility complex (MHC)-I signalling pathway ( 34 , 35 ). The antigen-promoting properties of TAPBP identified in several studies correlated with CD8 + cytotoxic T lymphocyte infiltration, mediating inflammatory injury ( 34 , 36 ).…”