Molecular Chimeric Recipient Precursor T Cells Promote Cardiac Allograft Survival in Mice

Abstract

Background: Molecular chimerism has become a potential method to induce donor-specific transplant tolerance. We researched the prolongation of cardiac allograft survival by recipient mouse molecular chimeric precursor T cells (pre-T cells) or hematopoietic stem cells (HSCs) infusion in vivo.

Methods: The donor C57BL/6 mouse MHC-I gene (H-2K(b) and H-2D(b) gene) were amplified by RT-PCR. The identified recipient BALB/c mouse pre-T cells and HSCs were transduced by the pMSCVneo retroviral vector of C57BL/6 mouse MHC-I gene (pMSCVneo-H-2D(b)/H-2K(b)). Then the molecular chimeric cells were transfused back to the BALB/c mice. Allogeneic T-lymphocyte proliferation was assessed in mixed lymphocyte reactions (MLR). A mouse model of heterotopic abdominal heart transplantation was performed to evaluate survival times and histological grade of acute rejection at 7 days after transplantation.

Results: BALB/c mice molecular chimeric pre-T cells and HSCs were cultured successfully after pMSCV-H-2D(b)/H-2K(b) transduction. After the molecular chimeric pre-T cell treatment, the result of MLR showed that the stimulating index of allogeneic T lymphocyte had a statistically significant decrease, which also exhibited a significant reduction after molecular chimeric HSC treatment. The survival time of cardiac allograft was prolonged after chimeric pre-T cell or HSC infusion; meanwhile, pathologic rejection grade decreased significantly. Nevertheless, molecular chimeric pre-T cells exhibited a longer median survival time.

Conclusion: The molecular chimeric recipient mouse pre-T cell or HSC infusion reduced spleen T cells' response to allogeneic T cells in vitro and delayed cardiac allograft rejection in vivo. Pre-T cells have more advantages than HSCs on the prolongation of mouse cardiac allograft survival.