Liver-Resident Memory CD8+ T Cells: Possible Roles in Chronic HBV Infection

Abstract

Achieving a functional cure for chronic hepatitis B virus (HBV) infection or complete elimination of HBV covalently closed circular DNA (cccDNA) has been challenging in the treatment of patients with chronic HBV infection. Although novel antivirals are being investigated, improving HBV-specific adaptive immune responses is also important for durable viral clearance. Tissue-resident memory CD8⁺ T (T_RM) cells were recently reported as a T-cell population that resides in peripheral tissues and does not recirculate. T_RM cells have been studied in the livers of mice and humans. Liver T_RM cells have distinct characteristics compared to T cells in peripheral blood or other tissues, which may be associated with the unique microenvironment of the liver. In this review, we describe the characteristics of liver T_RM cells and their implications in chronic HBV infection. We emphasize that liver T_RM cells can be an immunotherapeutic target for the treatment of chronic HBV infection.

Keywords: chronic HBV infection; liver-resident T cell; tissue-resident T cell.

Figure 1

Characteristics of tissue-resident memory T (T_RM) cells. T_RM cells express CD69 and CD103, though CD103 expression is variable depending on the type of peripheral organ. These cells also downregulate KLF2 and S1PR1 and cannot egress to the blood or secondary lymphoid organs; therefore, they reside in the peripheral tissues. T_RM cells do not express CCR7 and exhibit an effector memory T cell (T_EM) phenotype or effector memory T cells re-expressing CD45RA (T_EMRA) phenotype. However, circulating memory T cells also have central memory T (T_CM) cells that express CCR7 but not CD45RA. CM, central memory; EM, effector memory; EMRA, effector memory re-expressing CD45RA.