Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo

Permanent partial phenotypic correction and tolerance in a mouse model of hemophilia B by stem cell gene delivery of human factor IX

“…It is known that delivery of recipient BM cells transduced with foreign MHC class I or II results in tolerance to the donor antigen. [11][12][13][27][28][29][30] Although hFIX is a secreted antigen and will be presented as a set of self-restricted peptides, the elimination of mature hFIX reactive T cells from the donor population by lineage depletion may give the hFIX-expressing donor cells sufficient advantage to establish hFIX-specific mixed cell chimerism. Approximately 30% eGFP chimerism was present in all recipients of eGFP transduced cells, although no assessment of tolerance was made.…”

Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice

“…This concept has been extended to tolerance induction through the establishment of molecular chimerism by the transfer of class 1 or class 2 histocompatibility genes into the hematopoietic compartment. [13][14][15][16][17] In the present study, we have explored whether a similar approach can be applied for a model transgene but with a less toxic nonmyeloablative conditioning regimen in which bone marrow (BM) cells modified to express EGFP were transplanted in murine recipients pretreated with low doses of busulfan or treosulfan. In addition, the monitoring of EGFP expression in transplanted cells provides a valuable marker system for identifying those cell types that confer immunologic tolerance.…”

Gene Therapy Progress and Prospects: Gene therapy in organ transplantation

“…21,22 Recently, it has been shown that treatment of immunocompetent mice with nondepleting anti-T-cell antibodies together with syngeneic bone marrow infected with adenoviruses carrying an allogeneic MHC class I gene can lead to the acceptance of fully-allogeneic cardiac transplants which share the same MHC class I antigen carried by the adenovirus construct. 24 This approach essentially mimics results obtained using donor-specific transfusion, coupled with the use of nondepleting anti-Tcell antibodies to induce tolerance. Although the mechanism by which acceptance was achieved is unknown, transplant acceptance was observed even though gene expression was very short lived in vivo.…”