Lymphoid cells and granulocyte progenitors in early human fetal livers: immunological parameters and in vitro cellular interactions

: Human fetal liver (HFL) transplantations have been performed in infants with severe combined immunodeficiency and in patients with aplastic anemia, but the success rates have been extremely low, partly due to insufficient cell doses in grafts from a single donor. In order to explore the possible use of combining several HFL grafts from multiple donors, we studied immunological parameters as well as the in vitro responses of HFL cells from 20 fetuses, at 6 to 11 weeks of gestation, to allogeneic HFL cells and to adult lymphocytes in the mixed lymphocyte reaction (MLR), and the granulocyte-macrophage colony-forming cells (GM-CFC) assay. HFL cells of 6 to 11 weeks of gestation were found to lack populations of cells bearing surface markers of T- and B-lymphocytes and were capable of proliferating into lymphoid colonies. Virtually no MLR was found to allogeneic HFL cells or to adult lymphocytes [stimulation index (SI) 0.63 to 1.94], whereas adult lymphocytes responded normally to HFL cells (SI 3.9 to 62.0). Coculturing mixtures of allogeneic HFL cells in agar did not lead to suppression of the GM-CFC capacity of each liver. It appears that HFL at 6 to 11 weeks of gestation lack immunocompetent cells capable of provoking positive MLR in response to allogeneic HFL cells or to adult lymphocytes, and also capable of inactivating HFL-derived hematopoietic stem cells. This model may represent an in vitro counterpart for the in vivo pooling of HFL cells from multiple donors performed in order to increase graft cell dosage in man.