Year 2
We are working on developing better treatments for patients with genetic stem cell disorders. Our strategy is to treat fetuses before birth with stem cell transplantation in order to induce tolerance to the foreign transplanted cells and avoid immunosuppression. We have noted that the mother’s immune system is involved in rejecting the cells that are transplanted into the fetus. We are now studying how the fetal immune system responds to the transplant. This year, we learned that, although the fetal immune system becomes tolerant to the transplanted cells by deleting T cells, it does not become tolerant by making regulatory T cells, which would be a more robust mechanism of tolerance. Therefore, the strategy of adding in more regulatory T cells may boost tolerance. We are also analyzing immune development in human patients who undergo fetal surgery. We have refined our assays to include the most relevant pathway by which maternal T cells recognize the foreign fetus and have found that, in addition to maternal T cells recognizing the fetus, fetal T cells are also capable of recognizing the mother. We are now understanding whether this recognition is enhanced after fetal surgery, which would indicate sensitization and possible rejection.