Virologists from LIH and the Universities of Antwerp and Ghent in Belgium underscored with a new study the effectiveness of CD8+ T lymphocytes in the control of Human Immunodeficiency Virus (HIV) infection. Their study is a step towards a better understanding how functional cure could be achieved in HIV patients taking daily medication to keep viral loads low.
HIV infection does not progress in the same way in every patient. Most HIV-positive patients belong to a patient category named “progressors”. They need to be constantly treated with combination antiretroviral therapy (cART) to suppress viremia, whereas a small proportion of patients, named “controllers”, is able to control the virus without treatment or after a limited period of cART.
The research team hypothesized that to achieve functional cure in progressors it may be beneficial to boost the viral suppressive capacity of CD8+ T lymphocytes, which is very low in these patients. CD8+ T cells are mainly known for their cytotoxic function but some subsets display non-cytotoxic activity suppressing HIV infection.
The researchers set up an in vitro viral inhibition assay in which CD8+ T cells from 36 progressor patients were stimulated with peptides from an immunogenic HIV protein. ‘The viral suppressive capacity of CD8+ T cells was enhanced by the peptides in a significant proportion of patients, a feature till now only observed during natural control of HIV-1’, tells Philipp Adams, PhD candidate in the HIV Clinical and Translational Research Group in LIH’s Department of Infection and Immunity and co-first author on the publication that resulted from the study. ‘Interestingly, we show that suppression correlates with higher expression of certain cell surface markers such as the immune checkpoint inhibitor PD-1 in subsets of CD8+ T cells’.
The study contributes to a better comprehension of the antiviral activity of CD8+ T cells, which may be the key to a functional cure for HIV. It was published in March 2019 in a research article in the specialised journal AIDS. An editorial comment by Dr John Zaunders, expert in HIV immunology, puts the study into context. Of note, the article was selected as the “Best Belgium HIV article in basic science” by BREACH, the Belgium Research on AIDS and HIV Consortium.
The research was funded by the Research Foundation Flanders, the Antwerp Diner for HIV/AIDS and LIH. Philipp Adams is supported by an AFR PhD grant from the Luxembourg National Research Fund (FNR).
Link to publication: In-vitro viral suppressive capacity correlates with immune checkpoint marker expression on peripheral CD8+ T cells in treated HIV-positive patients