Starved T Cells Enable Undercover Liver Infection by Hepatitis B

HEPATITIS B has been shown to stimulate processes that deprive the body’s immune cells of key nutrients that they need to function. The findings explain why the immune system cannot control hepatitis B virus (HBV) infection after it is established in the liver, potentially paving the way for curative treatments in the future.

The research, led by University College London (UCL), London, UK, also presents insights into controlling the immune system, proving a potential aid for organ transplantation and treating autoimmune diseases.

“Hepatitis B patients usually do not have symptoms for decades, so can carry the virus unknowingly and can spread it through childbirth, sexual contact, or contaminated needles,” said senior author Prof Mala Maini, Professor of Viral Immunology, Division of Infection and Immunity, Faculty of Medical Sciences, UCL. “Our work has shown that during this ‘silent phase’ of infection, specialised suppressor cells switch off the immune response by cutting off its food supply. This is one of the many ways the liver protects itself from inflammation and immune damage but at the same time, prevents elimination of pathogens like hepatitis B.

“If we could boost the immune system and counteract the liver’s suppressive effect, then the infection could potentially be cleared after a large ‘burst’ of immune activity. This might cause short-term damage to the liver, but would prevent the long-term damage from scarring and liver cancers that we see in chronic patients.”

Researchers compared blood samples from 138 chronic hepatitis B patients and 99 healthy controls, and examined liver tissue samples from 42 patients. They ascertained that patients in the silent phases of infection had high levels of granulocytic myeloid-derived suppressor cells (gMDSCs). These gMDSCs, which suppress T cells (immune cells) by cutting off their food supply, were discovered to assemble in the liver.

“The gMDSCs suppressed both the T cells that fight HBV and those that cause inflammation in the liver,” explained lead author Dr Laura Pallett, Research Associate, Division of Infection and Immunity. “So patients with more gMDSC tended to have less liver damage but were unable to control HBV. Women had higher levels of gMDSC than men, which fits with their 3-fold lower risk of developing liver inflammation from hepatitis B.”

These results highlight a possible use for suppressor cells such as gMDSCs in cases where the immune system attacks healthy tissue, including autoimmune diseases or immune rejection of donated organs.

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