New research from Radboud University Medical Center indicates that T cells, part of the adaptive immune system, can influence the memory of innate immune cells. It was previously thought that the memory in innate immune cells functioned on its own. This unexpected connection presents exciting new opportunities for treating a range of ailments. Studies conducted on mice reveal that if the interaction between T cells and the innate immune response is temporarily interrupted after an organ transplant, there is no need for immunosuppressive medications.
The adaptive immune system develops as a result of the infections individuals encounter. This type of immune response takes time to activate, is highly specific to pathogens, and employs memory cells. In contrast, the innate immune system reacts much more quickly to threats and acts as the body’s initial defense mechanism. Approximately a decade ago, it was found that innate immune cells also possess memory, enabling them to respond more effectively and rapidly to infections they have encountered before, a phenomenon known as trained immunity.
Previously, trained immunity was thought to operate independently among innate immune cells. However, recent findings from an international research team led by Raphaël Duivenvoorden and Maaike Jacobs at Radboudumc demonstrate that T cells from the adaptive immune system significantly influence trained immunity. This influence takes place through direct interactions between cells using the CD40 molecule.
Transplantation
This research opens up new avenues for treating various conditions associated with trained immunity, such as autoimmune diseases, cancer, cardiovascular problems, and those related to organ transplants. The researchers showed in a mouse model that a transplanted heart can be accepted for an extended period if the interaction between T cells and the innate immune system is temporarily blocked following transplantation.
In their experiments, the scientists utilized nanoparticles containing drugs that inhibit the CD40 signal. They administered three doses of these nanoparticles along with a single dose of the existing medication CTLA4-Ig during the first week after the heart transplant. This approach resulted in long-term acceptance of the transplanted heart, eliminating the need for additional immunosuppressive treatment.
Memory
The memory within the innate immune system is crucial for effective defense against pathogens. However, this memory can be detrimental in scenarios where the innate immune response becomes overly activated, such as in autoimmune diseases, cardiovascular issues, and during organ transplant procedures. Therefore, comprehending the molecular processes behind this memory is key to developing innovative therapies.
The findings of this study suggest that altering the memory of the innate immune system could serve as a promising new treatment strategy for organ transplants. Duivenvoorden concludes: “In the next few years, we plan to advance this research with the goal of implementing this treatment strategy in human patients.”
