Scientists at the Babraham Institute have demonstrated that two RNA binding proteins have the potential for a stronger immune response to influenza in mice. Their findings, published today in Nature Communications, demonstrate that the absence of these proteins changes the potential of T cells that arise at the start of an infection. Further research may lead to implications for therapies that harness the immune system and for vaccine design.
Researchers from the Turner lab focused on the activity of ZFP36 and ZFP36L1, which means that by studying mice without these RNA binding proteins, they realised that their absence in T cells during the initial phase of a viral infection leads to a superior cytotoxic immune response.
The ones lacking their RNA binding proteins in T cells showed signs of effective combating the infection more effectively than those with the antibodies present. They also transferred cells that lacked ZFP36 and ZFP36L1 into normal mice and found that even a small number of transferred T cells provided the same advantage when dealing with an influenza infection.
Despite the absence of RNA binding proteins in T cells, the results were incredible, according to Dr Georg Petkau, a postdoctoral researcher who led the work. One striking observation of our research is that although the absence of RNA binding proteins in T cells has resulted in stable accelerated differentiation and enhanced cytotoxicity, this does not result in clinical injury or tissue damage, which is often a logical consequence of overt cytotoxicity during an immune response.
The results of this research suggest that the absence of negative knock on effects might result in accelerated viral clearance and may result in a faster resolution of infection in young mice. It would be interesting to see if a large accumulation of memory cells that demonstrate increased cytotoxicity in absence of RNA binding proteins might become potentially dangerous with age. Understanding how these RNA binding proteins might thus aid in autoimmune disease formation in elderly individuals.
The priming of the immune response once a pathogen is identified is a critical step which greatly alters the course of an immune response; it is the point at which immune cells choose their weapons before they start to combat the infection. This is because by RNA binding proteins, the researchers hope to improve our approaches to vaccine design and cell therapies.
Using the RNA binding proteins, we want to investigate how the formation of immune memory is affected by the absence of RNA binding proteins, and how do the superior cytotoxic traits obtained early in the response be replicated and maintained in the memory phase? Dr Martin Turner, the director of the Immunology research programme, has done this by examining how the stable cytotoxic program is established early after activation.