New insights on the path to curing chronic HIV infections
Transmission electron microscopic image showing HIV-particles grown in co-culture with lymphocytes.
AIDS, an immunodeficiency disease caused by infection with the human immunodeficiency virus (HIV), is one of the ten leading causes of death worldwide. Thanks to antiviral therapies, the disease can be treated, but there is still no cure. A large-scale comparative study by scientists at the German Center for Infection Research (DZIF) and University Medical Center Hamburg-Eppendorf indicates a critical role of a group of specialised immune cells in suppressing the antiviral immune response of HIV-infected patients.
HIV predominantly infects cells of the immune system, in particular so-called regulatory T cells. Their function is to suppress overactivation of the immune system and thus prevent the development of autoimmune diseases. Regulatory T cells carry various proteins on their surfaces, including the enzymes CD39 and CD73. Their task is to convert immune response-activating molecules into immune response-suppressing substances.
In people with HIV infection, it is already known that expression of these enzymes on the surface of regulatory T cells and other immune cells changes in relation to disease parameters—for example, the number of viruses in the body. Previous studies have also shown that CD39-expressing T cells produce a messenger that inhibits other immune cells.
A research team now compared the expression of CD39 and CD73 enzymes on the surface of certain T cells, which can also act in a regulatory manner, between HIV-infected individuals in different stages of disease and therapy (with or without therapy with antiretroviral drugs) and healthy volunteers.
In the large-scale comparative cohort study, the researchers, led by Prof Schulze zur Wiesch of the German Center for Infection Research (DZIF) and the University Medical Center Hamburg-Eppendorf, found that the number of CD73-expressing T cells decreased and the number of CD39-expressing T cells increased during the course of HIV infection. Furthermore, the amount of CD39-expressing T cells correlated with the condition of the patients: the more CD39-expressing T cells they had, the worse their health.
"The results from our study indicate that CD39- and CD73-expressing T cells alter the immune response during disease development of chronic HIV infection," says Prof Schulze zur Wiesch. "As a result, these T cells prevent the patients' immune system from effectively fighting HI viruses" he adds.
Future studies might help to better understand the effects of changes in CD39 and CD73 expression on regulatory T cells, as well as the function of regulatory T cells in HIV, in order to develop long-term cures for infection with HIV.
