Hobit controls tissue residency of memory T cells

Tissue resident memory T cells, T_RM, represent newly recognized T cell population that play physiologically-relevant role in body's defense against reinfection. T_RM cells are local tissue surveyors and act as a first-line defense [alongside of innate immunity] against tissue invading pathogens. Beyond these information nothing much was known about T_RM cells.

Now, a new paper published in Science showed that transcription factor named Hobit is a master regulator of T_RM cell development.   

Using mouse HSV-1 model, the authors found that by day 30 post-infection, Hobit was selectively up-regulated in T_RM cells recovered from peripheral tissues, such as skin, but not in central lymphoid tissues such as spleen.

Using Hobit-KO T cells the authors were able to confirm that Hobit was indeed intimately involved in development of tissue-resident memory T_RM cells (memory stage, day 40+). Deficiency of another transcription factor, Blimp1, had an additive effect on T_RM cells formation when combined with Hobit deficiency. 

Interesting, Hobit, in combination with Blimp1, also controlled tissue residency of innate cells such NK and NKT cells.

In summary, this study revealed that transcription factor Hobit controls tissue residency of memory T cells, T_RM cells. These data should be considered in developing T cell-oriented vaccines, including cancer immunotherapy (one limitation of this study is that for some reason the authors failed to show actual virus protection data with the regard of Hobit or Hobit + Blimp1 DKO T cells. ).

David Usharauli 

CD8 T effector cells monitor liver tissue with the help of platelet scouts

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 T_E cells monitor liver for the presence of viral antigens. It appears that CD8 T_E are using platelets for docking on liver endothelial cells to initiate surveillance.

The authors showed that contrary to conventional thinking, initial docking of CD8 T_E cells on liver endothelial cells was antigen-independent in HBV infected hosts.

Next, the authors showed that this particular docking of CD8 T_E cells on liver endothelial cells was independent of known mechanisms involving integrins, selectins or chemokines.

Unexpectedly, initial docking of CD8 T_E 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 T_E cells on liver endothelial cells via platelets, CD8 T_E 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 T_E cells and platelets. It is not clear what signals promotes adhesion of CD8 T_E 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