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.
Piasecki
Julia C
JC
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Beagles
Karen
K
Beard
Brian C
BC
Riddell
Stanley
S
Kiem
Hans-Peter
HP
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D010215:Papio; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019076:Transgenes / Q000276:immunology*; D019172:Transplantation Conditioning
D018952:Antigens, CD34