A new study from scientists at Cincinnati Children’s suggests there may be a way to further protect transplanted hearts from rejection by preparing the donor organ and the recipient with an anti-inflammatory antibody treatment before surgery occurs.
The findings, published online in PNAS, focus on blocking an innate immune response that normally occurs in response to microbial infections. The same response has been shown to drive dangerous inflammation in transplanted hearts.
In the new study – in mice — transplanted hearts functioned for longer periods when the organ recipients also received the novel antibody treatment. Now the first of a complex series of steps has begun to determine whether a similar approach can be safely performed for human heart transplants.
„The anti-rejection regimens currently in use are broad immunosuppressive agents that make the patients susceptible to infections. By using specific antibodies, we think we can just block the inflammation that leads to rejection but leave anti-microbial immunity intact,“ says corresponding author Chandrashekhar Pasare, DVM, PhD, director of the Division of Immunobiology at Cincinnati Children’s.
Making memory T cells a bit more forgetful
The research team, which included first author Irene Saha, PhD, a research fellow in the Pasare Lab, and several colleagues at Cincinnati Children’s, zeroed in on how dendritic cells from the donor organ trigger an inflammatory response in the recipient’s body.
Specifically, the team found that memory CD4 T cells in the recipient activated donor dendritic cells through signals delivered by the proteins CD40L and TNF?. When this signaling pathway was blocked with gene editing techniques, the results included dampened inflammation and prolonged survival of transplanted hearts.
In the study, untreated mice rejected the donated heart within a week. But in mice that were gene edited to lack receptors for CD40L and TNF?, strong heart function persisted through day 66, when the experiment was terminated.
https://www.pnas.org/doi/10.1073/pnas.2401658121
