Study on Allograft Tolerance Using the Lung Transplantation Mouse Model in the United States

Dr. Robert M. Aris of North Carolina State University and colleagues published in a recent issue of the Journal of Thoracic Surgery that donor-specific infusion technology (DST) is used in combination with a chronic rejection mouse model of lung transplantation. Treatment with anti-CD154 monoclonal antibodies can induce long-term tolerance to transplanted organs. Dr. Aris and colleagues pointed out that the use of medical models to induce the development of transplanted organ tolerance studies will be an important achievement in the study of transplantation. At present, researchers are trying to convince the host that these new transplants are actually their own organs. The research significance has far exceeded the efficacy of routine use of suppressing immune rejection.

Donor-specific infusion techniques allow the host to develop tolerance only to the exogenous proteins carried by the transplanted organ, rather than all exogenous proteins that increase the risk of infection; anti-CD154 monoclonal antibody treatment can destroy T cells. The activation process. This combination therapy has proven to be a very effective induction program for immune tolerance in non-lung transplant models, including pancreas, heart, and skin grafts.

The researchers pointed out that in the chronic rejection model of lung transplantation, donor-specific infusion techniques combined with anti-CD154 can significantly prolong the survival time of histologically completely incompatible tracheal grafts (>100 days ), and do not need to apply immunosuppressive therapy.

Dr. Aris said that, surprisingly, the results of the experiment showed that the survival time of the graft is far beyond people's imagination, and it takes a lot of effort to conduct research. The combined treatment of this DST/anti-CD154 monoclonal antibody does not act in a mutually chimeric manner, but instead induces tolerance to transplantation through a peripheral mechanism. Among them, the peripheral mechanisms included significantly reduced cytotoxic T cell activity (p<0.001) and a significant increase in the proportion of CD4+ and CD25+ cell levels occupied (p=0.03).

Currently, researchers are making corrective experiments on the treatment strategy to make it more applicable to clinical requirements. In a recent study, researchers performed relevant treatments on experimental animals 7 days prior to transplant surgery. Dr. Aris explained that, in fact, this cannot happen in real life because donated organ donors can only be obtained within a few hours before transplant surgery. Therefore, researchers must consider whether this treatment can be closer to the actual clinical transplant surgery. At present, their research in this area has made some progress.

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