HEMATOPOIESIS Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD341 cells

population assay is the criterion for the study of self-renewal and multilineage differentiation of human hematopoietic stem cells. An important shortcoming of this model is the reported absence of T-cell development. We studied this as-pect of the model and investigated how it could be optimized to support T-cell devel-opment. Occasionally, low-grade thymic engraftment was observed in NOD/SCID mice or Rag22/2gc2/2 mice. In contrast, the treatment of NOD/SCID mice with a monoclonal antibody against the murine interleukin-2Rb, (IL-2Rb) known to de-crease natural killer cell activity, resulted in human thymopoiesis in up to 60 % of the mice. T-cell development was pheno-typically normal and resulted in poly-clonal, mature, and functional CD12 TCRab1 CD41 or CD81 single-positive T cells. In mice with ongoing thymopoiesis, peripheral T cells were observed. TREC analysis showed that T cells with a naive phenotype (CD45RA1) emerged from the thymus. In approximately half of these mice, the peripheral T cells included a pauciclonal outgrowth of CD45RO1 cells. These data suggest that all elements of a functional immune system were present in these animals. (Blood. 2002;99