Death and All Its Friends: The Role of Programmed Death-1 in T-cell Exhaustion During Chronic Viral Infection
Patwardhan, Utsav M.
MetadataShow full item record
Programmed Death-1 (PD-1) is a CD-28 family inhibitory immune receptor that is located on Tc cells, particularly during chronic infection. Its role in regulating the immune response is crucial because it ensures a middle ground between preventing self-immunity and ensuring immune efficacy. My topic focuses on T-cell exhaustion during chronic viral infection. Numerous studies have found that as the infection progresses, virus-specific T-cells increasingly show signs of exhaustion (lowered cytokine secretion and replicative ability and increased apoptosis). In infections such as HIV and hepatitis C, these signs are directly correlated to the increased expression of PD-1, which interacts with its ligands on antigen presenting cells: PD-L1 and PD-L2. The binding of the ligands to PD-1 has immune suppressant effects on the Tc cells by inhibiting the PI3k/Akt pathway. The three papers that I focus on address the role of PD-1 in increasing cell exhaustion during viral infection. All three also explore the role of additional receptors (CD 57 and CTLA-4) as co-factors with PD-1. The third paper, in particular, explores the role of HIV infection in upregulating PD-1 ligand expression on antigen-presenting cells, and the role of the PI3K/Akt pathway in this regard. This research has tremendous potential to combat HIV and other viruses, complementing anti-retroviral therapy. This possible medication, that blockades PD-1 and its co-receptors, could prevent the weakening of the immune system and help to slow viral replication by utilizing the body’s immune system to help fight disease progression.