ABSTRACT
Background and Objectives@#Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail. @*Methods@#and Results: Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton’s jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG 1 and IgG 2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220 ＋ GL7 ＋ ) and memory T cells (CD62L ＋ CD44 ＋ ) both in CD4 ＋ and CD8 ＋ subsets. Similar results were obtained for C57BL/6 mice. @*Conclusions@#hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity
ABSTRACT
Hepatitis C virus (HCV) is one of the main causes of liver disease. 1~2% of the Korean people has been reported to be infected by HCV. Although HCV is less infectious than hepatitis B virus (HBV), it is more prone to develop chronic infection (~ 80%) which may link to cirrhosis and hepatocellular carcinogenesis. In addition, prevalence of hepatitis caused by HCV infection is gradually increased every year in Korea. Recently, a large number of clinical trials using direct-acting antiviral (DAA) drugs have been shown efficient therapeutic results for chronic HCV infections and some of them are on the market. However, there is still a concern on viral evasion to the DAAs and the effective mechanisms of immunological clearance of HCV remains to be elucidated. Here, we introduce the recent findings on the role of Th17-Treg axis which may play a critical role of the viral pathogenesis and/or immunological defense against HCV infection. The underlying regulatory mechanisms of Th17-Treg axis might be a potential candidate for the better control of HCV chronic infections.