0000000000362023
AUTHOR
Christian Frenzel
Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer
Preparations of stress protein gp96 from tumor cells are active as tumor vaccines by eliciting immune responses against mixtures of individual tumor peptide antigens which are complexed to gp96. Due to the individual antigenicity of tumors, a vaccine consisting of tumor-derived gp96 has to be prepared individually for each patient from autologous tumor tissue. So far, gp96 expression by human tumors has not been analyzed. Here, we report stable and mostly homogenous expression of gp96 by colorectal cancer, which was enhanced compared to surrounding tumor stroma in 70% to 80% of colorectal cancer specimens. Fewer non-metastatic than metastatic primary cancer specimens showed enhanced gp96 ex…
Defective T helper response of hepatocyte-stimulated CD4 T cells impairs antiviral CD8 response and viral clearance.
Background & Aims: In hepatitis, hepatocytes gain the ability to express major histocompatibility complex (MHC) class II molecules and to present antigen to CD4 T cells. Here, we investigated whether MHC class II-expressing hepatocytes influence in vitro the differentiation of CD4 T cells and in vivo the T-cell response to and control of viral infection. Methods: Class II transactivator-transgenic hepatocytes that constitutively express MHC class II molecules were used to stimulate CD4 T cells in vitro, and the effector response type of the stimulated CD4 T cells was determined. The in vivo relevance of the obtained findings was confirmed by infecting nontransgenic or class II transactivato…
Cutting Edge: A Key Pathogenic Role of IL-27 in T Cell- Mediated Hepatitis
Abstract The signals driving T cell activation in T cell-mediated fulminant hepatitis are not fully understood. In this study, we identify the cytokine IL-27p28/EBI3 as a major pathogenic factor in the ConA model of T cell-mediated hepatitis. We found an up-regulation of hepatic EBI3 and p28 expression and augmented levels of IL-27 in wild-type mice after ConA administration, suggesting a potential pathogenic role of this cytokine in ConA hepatitis. Consistently, IL-27 EBI3-deficient mice were almost completely protected from ConA-induced liver damage. Such protection was associated with reduced levels of IFN-γ and its signaling proteins pSTAT-1 and T-bet. Finally, in vivo blockade of IL-27…
Murine liver antigen presenting cells control suppressor activity of CD4+CD25+ regulatory T cells.
CD4(+)CD25(+) regulatory T cells (Treg) are important mediators of peripheral immune tolerance; however, whether Treg participate also in hepatic immune tolerance is not clear. Therefore, we tested the potential of Treg to suppress stimulation of CD4(+) T cells by liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC), or hepatocytes. In the absence of Treg, all 3 types of liver cells could stimulate CD4(+) T cell proliferation; in the presence of Treg, however, CD4(+) T cell proliferation was suppressed. Interaction with KC even stimulated the expansion of the Treg population; LSEC or hepatocytes, in contrast, could not induce proliferation of Treg. Because liver inflammation can be…