The use of microparticles（MPs） as adjuvants has attracted increasing interest in vaccine delivery systems.Many physiochemical characteristics of MPs including hydrodynamic size,surface properties,and morphology can ...The use of microparticles（MPs） as adjuvants has attracted increasing interest in vaccine delivery systems.Many physiochemical characteristics of MPs including hydrodynamic size,surface properties,and morphology can regulate the immune response.Surface charge is an important characteristic of MPs,but how it affects their adjuvanticity remains unknown.In this study,we prepared uniform-sized polylactide MPs coated with various polymers of different positive charge,and investigated how the surface charge affected antigen loading and macrophage phagocytosis and activation in vitro.A higher surface charge greatly enhanced antigen loading and antigen internalization into macrophages,promoted the expression of MHC 11 and CD80,and increased the secretion level of TNF-a.Taken together,these results indicated that surface charge was an important parameter for improving the adjuvanticity of MPs.展开更多
Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral im...Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8＋ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin （Ova） as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.展开更多
基金financially supported by the Special Fund for Agroscientific Research in the Public Interest(Grant No.201303046)the 973 Program(Grant No.2013C13531500)the Knowledge Innovation Program of the Chinese Academy of Sciences(Grant No.KSCX2-EW-R-19)
文摘The use of microparticles（MPs） as adjuvants has attracted increasing interest in vaccine delivery systems.Many physiochemical characteristics of MPs including hydrodynamic size,surface properties,and morphology can regulate the immune response.Surface charge is an important characteristic of MPs,but how it affects their adjuvanticity remains unknown.In this study,we prepared uniform-sized polylactide MPs coated with various polymers of different positive charge,and investigated how the surface charge affected antigen loading and macrophage phagocytosis and activation in vitro.A higher surface charge greatly enhanced antigen loading and antigen internalization into macrophages,promoted the expression of MHC 11 and CD80,and increased the secretion level of TNF-a.Taken together,these results indicated that surface charge was an important parameter for improving the adjuvanticity of MPs.
文摘Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8＋ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8＋ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin （Ova） as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.
