Liver is a body's chemical detox factory. Several viruses including HBV can infect liver cells called hepatocytes. What is interesting about HBV that it is essentially a non-cytopathic virus in immunocompetent hosts, meaning that it can infect hepatocytes and does no "damage" to it (unlike, for example, influenza virus infection of airway epithelial cells). More likely, due to continuing immunosurveillance of liver tissue by innate immune cells, like NKT and NK cells, liver cells showing obvious abnormalities are quickly eliminated.
But what about adaptive immune system? New study in journal Cell explains how CD8 TE cells monitor liver for the presence of viral antigens. It appears that CD8 TE are using platelets for docking on liver endothelial cells to initiate surveillance.
The authors showed that contrary to conventional thinking, initial docking of CD8 TE cells on liver endothelial cells was antigen-independent in HBV infected hosts.
Next, the authors showed that this particular docking of CD8 TE cells on liver endothelial cells was independent of known mechanisms involving integrins, selectins or chemokines.
Unexpectedly, initial docking of CD8 TE cells on liver endothelial cells was reduced by platelet depletion or when adoptively transferred platelets lacked CD44 expression (CD44 interacts with hyaluronan).
The authors showed that after initial Ag-independent docking of CD8 TE cells on liver endothelial cells via platelets, CD8 TE cells subsequent liver tissue monitoring and effector function (crawling cessation and IFN-γ secretion) was Ag-dependent events.
In summary, this study described novel mechanism of cell-cell cooperation between CD8 TE cells and platelets. It is not clear what signals promotes adhesion of CD8 TE cells to platelets. It is not even clear why platelets are adhering to liver sinusoidal endothelial cells in the first place. Are platelets sensing subtle changes in liver tissue due to non-cytopathic HBV infection?
David Usharauli
Next, the authors showed that this particular docking of CD8 TE cells on liver endothelial cells was independent of known mechanisms involving integrins, selectins or chemokines.
Unexpectedly, initial docking of CD8 TE cells on liver endothelial cells was reduced by platelet depletion or when adoptively transferred platelets lacked CD44 expression (CD44 interacts with hyaluronan).
The authors showed that after initial Ag-independent docking of CD8 TE cells on liver endothelial cells via platelets, CD8 TE cells subsequent liver tissue monitoring and effector function (crawling cessation and IFN-γ secretion) was Ag-dependent events.
In summary, this study described novel mechanism of cell-cell cooperation between CD8 TE cells and platelets. It is not clear what signals promotes adhesion of CD8 TE cells to platelets. It is not even clear why platelets are adhering to liver sinusoidal endothelial cells in the first place. Are platelets sensing subtle changes in liver tissue due to non-cytopathic HBV infection?
David Usharauli
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