An investigation into the role of LAP+CD8+ T cells in the chronic hepatitis C patients

• Main Authors: Kai Sheng Ko, 柯凱升
• Other Authors: C. Y. Lin
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/65699718998291862386

碩士 === 長庚大學 === 生物醫學研究所 === 100 === Abstract Chronic hepatitis C is a serious health issue that claims a lot of mortality in the whole wide world. Following infection with the hepatitis C virus (HCV). In most cases, immunity fails to eradicate the virus, resulting in slowly progressing immunopathology in the HCV-infected liver. The exhausted anti-HCV T cells responses that are hurdled by strong regulatory immune responses are the underlying mechanisms for this progressive immunopathology. A newly defined subset of CD8+ T cells that express latency-associated peptide (LAP) on their cell surface (LAP+CD8+ T cells) exhibit regulatory activity and is deemed as one of the suppressive T cells. In my study, it had been shown that the percentage of LAP+CD8+ T cells in peripheral blood of HCV patients was significantly increased when compared with healthy volunteers, and these cells had significantly lower percentage of naive T cells and higher percentage of Tem cells. Furthermore, the phenotype analysis indicated that LAP+CD8+ T cells were highly activated when compared with LAP-CD8+ T cells and expressed increased levels of CD25, CD161, CD38 and HLA-DR. These LAP+CD8+ T cells from patients with chronic hepatitis C were still suppressors and could partially suppress the proliferation of CD4+CD25- T cells. In addition, LAP+CD8+ T cells could accumulate more in the liver tissue than in peripheral blood. Interestingly, these LAP+CD8+ T cells included HCV-specific and non-HCV-specific cells as documented by pentamer assay. Furthermore, the T cells were stimulated by TLR4 agonist (HMGB1) combined with anti-CD3, perhaps causing increased LAP+CD8+ T cells in the peripheral blood of HCV patients. Moreover, percentage of LAP+CD8+ T cells were significant correlation with ALT level in patients with chronic hepatitis C and healthy volunteers. Based on these results, I suggested that LAP+CD8+ T cells included HCV-specific and non-HCV-specific cells, and accumulated in the liver tissue, is one of the suppressive T cells that impair the anti-HCV immune responses in patients with chronic hepatitis C.