Back A novel immunotherapy may improve the treatment of HIV when regulatory T cells collaborate
A novel immunotherapy may improve the treatment of HIV when regulatory T cells collaborate
A study led by the Infection Biology Group at Pompeu Fabra University points to regulatory T cells as an important component for fighting HIV infection.
Chronic HIV infection results in the exhaustion of the immune system, a phenomenon characterized by dysfunctional T cells. The exhausted T cells display inhibitory proteins on their surface that could be the key to restoring the immune function in cases of immunosuppression. Andreas Meyerhans, leader of the Infection Biology Group of the Department of Experimental and Health Sciences (DCEXS) at Pompeu Fabra University (UPF), is leading a research study that suggests that interfering with the negative signals transmitted by such proteins could improve the medical treatment against the human immunodeficiency virus. The results appear in an article signed by Cristina Peligero and published on 3 December in PLOS Pathogens.
The human immune system consists of a complex network of positive and negative regulators that jointly orchestrate the response to pathogenic threats. A newly HIV-infected individual develops a vivid immune response restricting virus expansion. At the same time, so-called regulatory T cells keep the effector response in check avoiding an overreaction of immune cells that would damage the individual’s tissues and organs. As the infection continues and it becomes clear that the virus will not be eliminated from the infected host, many of the effector T cells are put to sleep by the mechanism known as exhaustion. Since the cellular communication pathway PD-1/PD-L1 is implied in the exhaustion of the regulatory T cells, Dr. Meyerhans’ group decided to investigate what happens when waking up exhausted T cells by blocking the PD-1/PD-L1 pathway. In collaboration with clinicians led by Felipe Garcia (Hospital Clinic) and Hernando Knobel (Hopital del Mar), blood cells from HIV-infected individuals were isolated and tested for their response after wake-up with antibodies against PD-L1.
Both effector T cells and regulatory T cells were woken up, but the extent to which this occurred was dependent on the virus load of the individuals. “When the virus load was low and thus well controlled by medication, for example, then especially the effector T cells expanded”, explains Cristina Peligero, the first author of the study. “However, in samples where the virus is not medically controlled, then regulatory T cells expanded greatly and led to further virus expansion thus having a detrimental effect”. Together these observations may have important consequences when it comes to the use of such antibodies as therapeutics. Only HIV-infected individuals whose virus load is well controlled might get a boost in their antiviral immune responses generating a beneficial host-over-virus balance.
Trials with anti-PD-L1 antibodies, also called immune checkpoint inhibitors, are being designed to combat chronic virus infections and have started to fight cancers better. The work from the Meyerhans group now points to regulatory T cells as an important component in the game worthy of consideration.
Cristina Peligero presented this work at the 4th European Congress of Immunology in Vienna on 7 September 2015. She obtained the “EFIS-Biolegend Bright Sparks Award” for her outstanding oral presentation.
Reference work: Cristina Peligero, Jordi Argilaguet, Roberto Güerri-Fernandez, Berta Torres, Carmen Ligero, Pilar Colomer, Montserrat Plana, Hernando Knobel, Felipe García and Andreas Meyerhans. PD-L1 Blockade Differentially Impacts Regulatory T Cells from HIV-Infected Individuals Depending on Plasma Viremia. Plos Pathogens, December 2015.