AN INNOVATIVE new study has uncovered a protein that is fundamental to controlling immune responses, which could provide much needed clarification of why immune T cells fail to eradicate some tumours and chronic infections.
T cells function to identify and destroy infectious bacteria, viruses, and cells that can trigger the development of tumours. When the immune system is threatened, T cells act on control signals from other immune cells, therefore adapting to the specific nature of the invasion. However, these responses often fail and it is this particular occurrence that has driven a recent study to pinpoint the activity of T cells. The researchers, led by Prof Linda Bradley, Immunity and Pathogenesis Program, Sanford Burnham Prebys Medical Discovery Institute, California, USA, observed T cell activity with the aim of shedding new light on the development of chronic diseases.
“We discovered that a protein on the surface of T cells, P-selectin glycoprotein ligand 1 (PSGL1), acts as a negative regulator of T cell function. PSGL1 has the broad capacity to dampen T cell signals and promote the exhaustion of T cells in viral and tumour mouse models,” remarked Prof Bradley. When the theory was tested on mice that were bred to lack PSGL1, it was found that T cells remained active for a considerably longer period of time and subsequently eliminated lymphocytic choriomeningitis virus. When the same mice were injected with melanoma cells, tumour growth was stunted. The results therefore indicated that PSGL1 functions to regulate T cell responses, a breakthrough that could transform the way that diseases and infections are treated.
Significantly, the study demonstrates that the use of PSGL1 could have multifaceted treatment benefits for a number of chronic conditions. Prof Bradley suggested that entirely blocking the protein could improve immune response to cancer and viral infections, namely hepatitis. In addition, increasing the level of PSGL1 may obstruct immune response which could prove highly effective for treating autoimmune diseases. Following this successful discovery, the team of researchers are now embarking on an investigation into how the PSGL1 target might work alongside existing anti-cancer drugs to maximise the impact of immunotherapy.