Induction of Transgene-Specific Cytotoxic T Lymphocyte Responses After Transplantation of Gene-Modified CD34+ Cells Despite Nonablative Immunosuppressive Conditioning

In previous studies we showed that low-dose irradiation and immunosuppression with cyclosporine and mycophenolate mofetil prolonged in vivo persistence of gene-modified T cells but was unable to induce tolerance. We hypothesized that the lack of sustained antigen presentation because of the limited life span of the infused T cells might be responsible for the lack of tolerance induction. Thus, we examined whether tolerance could be induced by infusion of long-lived stem cells. Two baboons were transplanted with YFP/neo-transduced CD34+ cells. The transgene-marked cells disappeared completely within 5 weeks and CD8+ transgene-specific cytotoxic T lymphocytes were detected in both animals. Thus, this nonablative conditioning regimen did not provide sufficient immunosuppression for the induction of tolerance after infusion of gene-modified CD34+ cells.