Hepatitis B virus ‐specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV‐infected hepatocytes in mice

Here, we detected stem cell memory T cells (TSCMs) in chronic hepatitis B virus (HBV)-infected patients, using HBV core and polymerase peptide HLA tetramers. When these TSCMs were transferred into the human hepatocyte-transplanted, HBV-infected TK-NOG mouse, they differentiated into cytotoxic T lymphocytes, produced interferon gamma and interleukin-2, and developed histologically proven hepatitis. Furthermore, HBV DNA and human albumin in mouse serum declined and human hepatocytes were eliminated in the mouse model. Chronic infection with the hepatitis B virus (HBV) induces progressive hepatic impairment. Achieving complete eradication of the virus remains a formidable challenge. Cytotoxic T lymphocytes, specific to viral antigens, either exhibit a numerical deficiency or succumb to an exhausted state in individuals chronically afflicted with HBV. The comprehension of the genesis and dissemination of stem cell memory T cells (TSCMs) targeting HBV remains inadequately elucidated. We identified TSCMs in subjects with chronic HBV infection and scrutinized their efficacy in a murine model with human hepatocyte transplants, specifically the TK-NOG mice. TSCMs were discerned in all subjects under examination. Introduction of TSCMs into the HBV mouse model precipitated a severe necro-inflammatory response, resulting in the elimination of human hepatocytes. TSCMs may constitute a valuable tool in the pursuit of a remedial therapy for HBV infection.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research