Cell exhaustion in HIV-1 infection: role of suppressor cells

Suppressor cells regulate immune responses during chronic viral infection by limiting immunopathology associated with inflammation and immune activation. This dampening of adaptive immune responses can be harmful in HIV-1 infection as it also prevents the immune system from clearing the virus, leading to viral persistence and prolonged antigen expression that often leads to immune exhaustion. A current priority is to find the best strategy to target and manipulate key molecules such as CD39 that suppress anti-HIV-1 immune responses.

New suppressor cell subsets and cellular markers have been identified and characterized in the past years. We are able to identify and measure regulatory T cells, regulatory B cells and myeloid-derived suppressor cells in HIV-1-infected patients. We can also measure antigen-specific regulatory T cells in patients, which is a valuable step forward. Targeting HIV-1-specific regulatory T cells could be beneficial if we aim to manipulate key inhibitory molecules such as CTLA-4 and/or PD-1 that have already proven their efficacy in cancer. New other possible targets to take into account are CD39 and Tim-3-Gal9 pathways that have recently attracted attention in the field. These new findings offer the possibility to recognize suppressor cells as future targets in therapeutic vaccines because it became obvious that good vaccines candidates should concurrently generate robust effector responses and inhibit specific pathways that lead to immune suppression and exhaustion.

The recent advances on suppressor cells and the availability of new markers or assays will certainly open up new avenues for targeting molecules that are involved in immune suppression pathways, thus avoiding viral persistence and immune exhaustion.